The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Ji Ming Wang - One of the best experts on this subject based on the ideXlab platform.
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the Formylpeptide Receptor 2 fpr2 and its endogenous ligand cathelin related antimicrobial peptide cramp promote dendritic cell maturation
Journal of Biological Chemistry, 2014Co-Authors: Keqiang Chen, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Jiaqiang Huang, Yi Xiang, Qun Jiang, Ji Ming WangAbstract:Mouse Formylpeptide Receptor 2 (Fpr2) is a homologue of the human G-protein coupled chemoattractant Receptor FPR2, which interacts with pathogen and host-derived chemotactic agonists. Our previous studies revealed reduced allergic airway inflammation and immune responses in Fpr2-deficient (Fpr2(-/-)) mice in association with diminished dendritic cell (DC) recruitment into the airway and draining lymph nodes. These defects prompted us to investigate the potential changes in the differentiation and maturation of DCs caused by Fpr2 deficiency. Bone marrow monocytes from Fpr2(-/-) mouse mice incubated with GM-CSF and IL-4 in vitro showed normal expression of markers of immature DCs. However, upon stimulation with the TLR4 agonist LPS, Fpr2(-/-) mouse DCs failed to express normal levels of maturation markers with reduced production of IL-12 and diminished chemotaxis in response to the DC homing chemokine CCL21. Fpr2(-/-) DCs also failed to induce allogeneic T-cell proliferation in vitro, and their recruitment into the T-cell zones of the spleen was reduced after antigen immunization. The capacity of Fpr2 to sustain normal DC maturation was dependent on its interaction with an endogenous ligand CRAMP expressed by DCs, because neutralization of either Fpr2 or CRAMP inhibited DC maturation in response to LPS. We additionally observed that the presence of exogenous CRAMP in culture increased the sensitivity of WT mouse DCs to LPS stimulation. The importance of CRAMP for DC maturation was further demonstrated by the observations that DCs from CRAMP(-/-) mice expressed lower levels of costimulatory molecules and MHC II and exhibited poor chemotaxis in response to CCL21 after LPS stimulation. Our observations indicate a nonredundant role for Fpr2 and its agonist CRAMP in DC maturation in immune responses.
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50 Cellular & Molecular Immunology The Grape Component Resveratrol Interferes with the Function
2014Co-Authors: Hengyi Tao, Wanghua Gong, Ye Zhou, Xia Zhang, Pablo Iribarren, Yuqing Zhao, Ji Ming WangAbstract:Resveratrol (3, 5, 4'-trihydroxystilbene) (RV) is a constituent of grape seeds with anti-inflammatory and anti-oxidant activities. In this study, we examined the capacity of RV to modulate the function of G protein-coupled chemoattractant Receptors, which play important roles in inflammation and immune responses. RV, over a non-cytotoxic concentration range, inhibited chemotactic and calcium mobilization responses of phagocytic cells to selected chemoattractants. At low micromolar concentrations RV potently reduced superoxide anion production by phagocytic leukocytes in response to the bacterial chemotactic peptide fMLF, a high affinity ligand for Formylpeptide Receptor FPR, and Aβ42, an Alzheimer's disease-associated peptide and a ligand for the FPR variant FPRL1. In addition, RV reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and the activation of nuclear factor NF-κB induced by Formylpeptide Receptor agonists. These results suggest that the inhibition of the function of chemoattractant Receptors may contribute to the anti-inflammatory properties of RV. Thus, RV may be therapeutically promising for diseases in which activation of Formylpeptide Receptors contributes to the pathogenic processes. Cellular & Molecular Immunology. 2004
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signal relay by cc chemokine Receptor 2 ccr2 and Formylpeptide Receptor 2 fpr2 in the recruitment of monocyte derived dendritic cells in allergic airway inflammation
Journal of Biological Chemistry, 2013Co-Authors: Keqiang Chen, Mingyong Liu, Ying Liu, Chunyan Wang, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Ji Ming WangAbstract:Chemoattractant Receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine Receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in Formylpeptide Receptor Fpr2 (Fpr2−/−). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2−/− mice, in the inflamed airway of CRAMP−/− mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung. Background: Chemoattractant Receptor Fpr2 interacts with host-derived agonists and mediates leukocyte trafficking. Results: In the lung of allergic inflammation, chemokine Receptor CCR2 elicits accumulation of monocyte-derived DC in perivascular region, but Fpr2 is critical for cell trafficking to peribronchiolar area. Conclusion: CCR2 and Fpr2 sequentially guide DC trafficking in inflamed lung. Significance: DC trafficking is controlled by multiple chemoattractant Receptors, which are potential therapeutic targets.
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signal relay by cc chemokine Receptor 2 ccr2 and Formylpeptide Receptor 2 fpr2 in the recruitment of monocyte derived dendritic cells in allergic airway inflammation
Journal of Biological Chemistry, 2013Co-Authors: Keqiang Chen, Mingyong Liu, Ying Liu, Chunyan Wang, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Ji Ming WangAbstract:Abstract Chemoattractant Receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine Receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in Formylpeptide Receptor Fpr2 (Fpr2−/−). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2−/− mice, in the inflamed airway of CRAMP−/− mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung.
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production of angiogenic factors by human glioblastoma cells following activation of the g protein coupled Formylpeptide Receptor fpr
Journal of Neuro-oncology, 2008Co-Authors: Yifang Ping, Ji Ming Wang, Jianhong Chen, Dailun Chen, Chengping Xu, Jiang Zheng, Xiuwu BianAbstract:Activation of the Formylpeptide Receptor (FPR), a G-protein-coupled Receptor, by its chemotactic peptide ligand N-formylmethionyl-leucyl-phenylalanine (fMLF) promotes the directional migration and survival of human glioblastoma cells. fMLF also stimulates glioblastoma cells to produce biologically active VEGF, an important angiogenic factor involved in tumor progression. In this study, we examined the capacity of FPR to regulate the production of another angiogenic factor, the chemokine IL-8 (CXCL8), in addition to its demonstrated ability to induce VEGF secretion by malignant glioma cells. We showed that the human glioblastoma cell line U87 secreted considerable levels of IL-8 (CXCL8) upon stimulation by the FPR agonist peptide fMLF. Tumor cells transfected with small interference (si)RNA targeting FPR failed to produce IL-8 as well as VEGF in response to fMLF. Glioblastoma cells bearing FPR siRNA exhibited reduced rate of tumorigenicity in nude mice and tumors formed by such tumor cells showed less active angiogenesis and lower level expression of both IL-8 and VEGF. These results suggest that FPR plays an important role in the angiogenesis of human malignant gliomas through increasing the production of angiogenic factors by FPR positive tumor cells.
Keqiang Chen - One of the best experts on this subject based on the ideXlab platform.
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Citing Articles
2016Co-Authors: Keqiang Chen, Xiuwu Bian, O. Zack M. Howard, Jian Huang, Behavior Human, Glioblastoma CellsAbstract:the epidermal growth factor Receptor by Formylpeptide Receptor exacerbates the malignant beha..
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the Formylpeptide Receptor 2 fpr2 and its endogenous ligand cathelin related antimicrobial peptide cramp promote dendritic cell maturation
Journal of Biological Chemistry, 2014Co-Authors: Keqiang Chen, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Jiaqiang Huang, Yi Xiang, Qun Jiang, Ji Ming WangAbstract:Mouse Formylpeptide Receptor 2 (Fpr2) is a homologue of the human G-protein coupled chemoattractant Receptor FPR2, which interacts with pathogen and host-derived chemotactic agonists. Our previous studies revealed reduced allergic airway inflammation and immune responses in Fpr2-deficient (Fpr2(-/-)) mice in association with diminished dendritic cell (DC) recruitment into the airway and draining lymph nodes. These defects prompted us to investigate the potential changes in the differentiation and maturation of DCs caused by Fpr2 deficiency. Bone marrow monocytes from Fpr2(-/-) mouse mice incubated with GM-CSF and IL-4 in vitro showed normal expression of markers of immature DCs. However, upon stimulation with the TLR4 agonist LPS, Fpr2(-/-) mouse DCs failed to express normal levels of maturation markers with reduced production of IL-12 and diminished chemotaxis in response to the DC homing chemokine CCL21. Fpr2(-/-) DCs also failed to induce allogeneic T-cell proliferation in vitro, and their recruitment into the T-cell zones of the spleen was reduced after antigen immunization. The capacity of Fpr2 to sustain normal DC maturation was dependent on its interaction with an endogenous ligand CRAMP expressed by DCs, because neutralization of either Fpr2 or CRAMP inhibited DC maturation in response to LPS. We additionally observed that the presence of exogenous CRAMP in culture increased the sensitivity of WT mouse DCs to LPS stimulation. The importance of CRAMP for DC maturation was further demonstrated by the observations that DCs from CRAMP(-/-) mice expressed lower levels of costimulatory molecules and MHC II and exhibited poor chemotaxis in response to CCL21 after LPS stimulation. Our observations indicate a nonredundant role for Fpr2 and its agonist CRAMP in DC maturation in immune responses.
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signal relay by cc chemokine Receptor 2 ccr2 and Formylpeptide Receptor 2 fpr2 in the recruitment of monocyte derived dendritic cells in allergic airway inflammation
Journal of Biological Chemistry, 2013Co-Authors: Keqiang Chen, Mingyong Liu, Ying Liu, Chunyan Wang, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Ji Ming WangAbstract:Chemoattractant Receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine Receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in Formylpeptide Receptor Fpr2 (Fpr2−/−). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2−/− mice, in the inflamed airway of CRAMP−/− mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung. Background: Chemoattractant Receptor Fpr2 interacts with host-derived agonists and mediates leukocyte trafficking. Results: In the lung of allergic inflammation, chemokine Receptor CCR2 elicits accumulation of monocyte-derived DC in perivascular region, but Fpr2 is critical for cell trafficking to peribronchiolar area. Conclusion: CCR2 and Fpr2 sequentially guide DC trafficking in inflamed lung. Significance: DC trafficking is controlled by multiple chemoattractant Receptors, which are potential therapeutic targets.
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signal relay by cc chemokine Receptor 2 ccr2 and Formylpeptide Receptor 2 fpr2 in the recruitment of monocyte derived dendritic cells in allergic airway inflammation
Journal of Biological Chemistry, 2013Co-Authors: Keqiang Chen, Mingyong Liu, Ying Liu, Chunyan Wang, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Ji Ming WangAbstract:Abstract Chemoattractant Receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine Receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in Formylpeptide Receptor Fpr2 (Fpr2−/−). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2−/− mice, in the inflamed airway of CRAMP−/− mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung.
Philip M Murphy - One of the best experts on this subject based on the ideXlab platform.
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Brief Definitive Report N-Formylpeptides Induce Two Distinct Concentration Optima for Mouse Neutrophil Chemotaxis by Differential Interaction with Two N-Formylpeptide Receptor (FPR) Subtypes: Molecular Characterization of FPR2, a Second Mouse Neutrophil F
2013Co-Authors: K. Hartt, Philip M Murphy, Grant D Barish, Ji-liang GaoAbstract:The N-Formylpeptide Receptor (FPR) is a G protein–coupled Receptor that mediates mammalian phagocyte chemotactic responses to bacterial N-Formylpeptides. Here we show that a mouse gene named Fpr-rs2 encodes a second N-Formylpeptide Receptor subtype selective for neutrophils which we have provisionally named FPR2. The prototype N-Formylpeptide fMLF induced calcium flux and chemotaxis in human embryonic kidney (HEK) 293 cells stably transfected with FPR2. The EC50s, �5 �M for calcium flux and chemotaxis, were �100-fold greater than the corresponding values for mouse FPR-transfected HEK 293 cells. Consistent with this, fMLF induced two distinct concentration optima for chemotaxis of normal mouse neutrophils, but only the high concentration optimum for chemotaxis of neutrophils from FPR knockout mice. Based on these data, we hypothesize that high- and low-affinity N-Formylpeptide Receptors, FPR and FPR2, respectively, may function in vivo as a relay mediating neutrophil migration through the high and low concentration portions of N-Formylpeptide gradients. Key words: chemoattractant • inflammation • neutrophil • G protein–coupled Receptor • phagocyt
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Reduced Fear Memory and Anxiety-like Behavior in Mice Lacking Formylpeptide Receptor 1
Behavior Genetics, 2011Co-Authors: Ji-liang Gao, Erich H. Schneider, Eugene L. Dimitrov, Forrest Haun, Therese M. Pham, Abdul H. Mohammed, Ted B. Usdin, Philip M MurphyAbstract:N -Formylpeptide Receptor 1 (FPR1) is a G protein-coupled Receptor that mediates pro-inflammatory chemotactic responses by phagocytic leukocytes to N -Formylpeptides produced by bacteria or mitochondria. Mice lacking Fpr1 ( Fpr1 ^−/− mice) have increased susceptibility to challenge with certain bacteria. FPR1 is also a Receptor for annexin-1, which mediates the anti-inflammatory effects of glucocorticoids as well as negative feedback by glucocorticoids of the hypothalamic-pituitary-adrenocortical axis. However, homeostatic functions of FPR1 in the neuroendocrine system have not previously been defined. Here we show that in systematic behavioral testing Fpr1 ^−/− mice exhibited increased exploratory activity, reduced anxiety-like behavior, and impaired fear memory, but normal spatial memory and learning capacity. Consistent with this, the homeostatic serum level of corticosterone in Fpr1 ^−/− mice was significantly lower compared with wild-type mice. The data implicate Fpr1 in modulation of anxiety-like behavior and fear memory by regulating glucocorticoid production.
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n Formylpeptides induce two distinct concentration optima for mouse neutrophil chemotaxis by differential interaction with two n Formylpeptide Receptor fpr subtypes molecular characterization of fpr2 a second mouse neutrophil fpr
Journal of Experimental Medicine, 1999Co-Authors: Jennifer K Hartt, Philip M Murphy, Grant D Barish, Ji-liang GaoAbstract:The N-Formylpeptide Receptor (FPR) is a G protein-coupled Receptor that mediates mammalian phagocyte chemotactic responses to bacterial N-Formylpeptides. Here we show that a mouse gene named Fpr-rs2 encodes a second N-Formylpeptide Receptor subtype selective for neutrophils which we have provisionally named FPR2. The prototype N-Formylpeptide fMLF induced calcium flux and chemotaxis in human embryonic kidney (HEK) 293 cells stably transfected with FPR2. The EC(50)s, approximately 5 microM for calcium flux and chemotaxis, were approximately 100-fold greater than the corresponding values for mouse FPR-transfected HEK 293 cells. Consistent with this, fMLF induced two distinct concentration optima for chemotaxis of normal mouse neutrophils, but only the high concentration optimum for chemotaxis of neutrophils from FPR knockout mice. Based on these data, we hypothesize that high- and low-affinity N-Formylpeptide Receptors, FPR and FPR2, respectively, may function in vivo as a relay mediating neutrophil migration through the high and low concentration portions of N-Formylpeptide gradients.
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Impaired antibacterial host defense in mice lacking the N-Formylpeptide Receptor
1999Co-Authors: Ji-liang Gao, Eric J. Lee, Philip M MurphyAbstract:N-Formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific Receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N-Formylpeptide Receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. Here we test this hypothesis in mice lacking the high affinity N-Formylpeptide Receptor (FPR), created by targeted gene disruption. FPR �� � mice developed normally, but had increased susceptibility to challenge with Listeria monocytogenes, as measured by increased mortality compared with wild-type littermates. FPR �� � mice also had increased bacterial load in spleen and liver 2 d after infection, which is before development of a specific cellular immune response, suggesting a defect in innate immunity. Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N-Formylpeptide fMLF (formyl-methionyl-leucyl-phenylalanine) were both absent in FPR �� � mice. These results indicate that FPR functions in antibacterial host defense in vivo. Key words: chemotaxis • Listeria • inflammation • chemoattractant • neutrophi
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a high potency nonformylated peptide agonist for the phagocyte n Formylpeptide chemotactic Receptor
Journal of Experimental Medicine, 1994Co-Authors: Elmer L. Becker, Natesa Muthukumaraswamy, Richard J. Freer, Philip M MurphyAbstract:Analysis of synthetic tri- and tetrapeptides has previously indicated that N-formylation is required for high biological activity when they react with the phagocyte N-Formylpeptide Receptor, suggesting that the natural ligand for the Receptor is from bacterial and/or mitochondrial sources. To explore this requirement further, we synthesized the pentapeptide methionyl-norleucyl-leucyl-phenylalanyl-phenylalanine (MNleLFF) and studied the effects of different NH2-terminal modifications on its activity. N-formyl-MNleLFF induced transient alterations of [Ca2+]i and superoxide production in human neutrophils with 10- and 100-fold greater potency, respectively, than the proto-type N-Formylpeptide, N-formylmethionyl-leucyl-phenylalanine (fMLF). Surprisingly, N-acetyl-MNleLFF was a potent as N-formyl-MNleLFF. Moreover, the unacylated counterpart H-MNleLFF was also highly active, having an EC50 for calcium mobilization of 10 nM, and for respiratory burst activation of 100 nM. All three pentapeptides could completely desensitize calcium transients elicited by stimulation of neutrophils with fMLF, whereas the neutrophil chemoattractants C5a and interleukin 8 only weakly affected fMLF-induced transients, suggesting that they activate neutrophils via the same Receptor as fMLF. Finally, all three pentapeptides activated the recombinant human N-Formylpeptide Receptor expressed in frog oocytes, but did not effectively activate related phagocyte Receptors. These data broaden the potential sources of natural ligands for the N-formyl-peptide Receptor from N-formylated bacterial and mitochondrial products to other nonformylated endogenous peptides.
Ji-liang Gao - One of the best experts on this subject based on the ideXlab platform.
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Brief Definitive Report N-Formylpeptides Induce Two Distinct Concentration Optima for Mouse Neutrophil Chemotaxis by Differential Interaction with Two N-Formylpeptide Receptor (FPR) Subtypes: Molecular Characterization of FPR2, a Second Mouse Neutrophil F
2013Co-Authors: K. Hartt, Philip M Murphy, Grant D Barish, Ji-liang GaoAbstract:The N-Formylpeptide Receptor (FPR) is a G protein–coupled Receptor that mediates mammalian phagocyte chemotactic responses to bacterial N-Formylpeptides. Here we show that a mouse gene named Fpr-rs2 encodes a second N-Formylpeptide Receptor subtype selective for neutrophils which we have provisionally named FPR2. The prototype N-Formylpeptide fMLF induced calcium flux and chemotaxis in human embryonic kidney (HEK) 293 cells stably transfected with FPR2. The EC50s, �5 �M for calcium flux and chemotaxis, were �100-fold greater than the corresponding values for mouse FPR-transfected HEK 293 cells. Consistent with this, fMLF induced two distinct concentration optima for chemotaxis of normal mouse neutrophils, but only the high concentration optimum for chemotaxis of neutrophils from FPR knockout mice. Based on these data, we hypothesize that high- and low-affinity N-Formylpeptide Receptors, FPR and FPR2, respectively, may function in vivo as a relay mediating neutrophil migration through the high and low concentration portions of N-Formylpeptide gradients. Key words: chemoattractant • inflammation • neutrophil • G protein–coupled Receptor • phagocyt
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Reduced Fear Memory and Anxiety-like Behavior in Mice Lacking Formylpeptide Receptor 1
Behavior Genetics, 2011Co-Authors: Ji-liang Gao, Erich H. Schneider, Eugene L. Dimitrov, Forrest Haun, Therese M. Pham, Abdul H. Mohammed, Ted B. Usdin, Philip M MurphyAbstract:N -Formylpeptide Receptor 1 (FPR1) is a G protein-coupled Receptor that mediates pro-inflammatory chemotactic responses by phagocytic leukocytes to N -Formylpeptides produced by bacteria or mitochondria. Mice lacking Fpr1 ( Fpr1 ^−/− mice) have increased susceptibility to challenge with certain bacteria. FPR1 is also a Receptor for annexin-1, which mediates the anti-inflammatory effects of glucocorticoids as well as negative feedback by glucocorticoids of the hypothalamic-pituitary-adrenocortical axis. However, homeostatic functions of FPR1 in the neuroendocrine system have not previously been defined. Here we show that in systematic behavioral testing Fpr1 ^−/− mice exhibited increased exploratory activity, reduced anxiety-like behavior, and impaired fear memory, but normal spatial memory and learning capacity. Consistent with this, the homeostatic serum level of corticosterone in Fpr1 ^−/− mice was significantly lower compared with wild-type mice. The data implicate Fpr1 in modulation of anxiety-like behavior and fear memory by regulating glucocorticoid production.
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n Formylpeptides induce two distinct concentration optima for mouse neutrophil chemotaxis by differential interaction with two n Formylpeptide Receptor fpr subtypes molecular characterization of fpr2 a second mouse neutrophil fpr
Journal of Experimental Medicine, 1999Co-Authors: Jennifer K Hartt, Philip M Murphy, Grant D Barish, Ji-liang GaoAbstract:The N-Formylpeptide Receptor (FPR) is a G protein-coupled Receptor that mediates mammalian phagocyte chemotactic responses to bacterial N-Formylpeptides. Here we show that a mouse gene named Fpr-rs2 encodes a second N-Formylpeptide Receptor subtype selective for neutrophils which we have provisionally named FPR2. The prototype N-Formylpeptide fMLF induced calcium flux and chemotaxis in human embryonic kidney (HEK) 293 cells stably transfected with FPR2. The EC(50)s, approximately 5 microM for calcium flux and chemotaxis, were approximately 100-fold greater than the corresponding values for mouse FPR-transfected HEK 293 cells. Consistent with this, fMLF induced two distinct concentration optima for chemotaxis of normal mouse neutrophils, but only the high concentration optimum for chemotaxis of neutrophils from FPR knockout mice. Based on these data, we hypothesize that high- and low-affinity N-Formylpeptide Receptors, FPR and FPR2, respectively, may function in vivo as a relay mediating neutrophil migration through the high and low concentration portions of N-Formylpeptide gradients.
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Impaired antibacterial host defense in mice lacking the N-Formylpeptide Receptor
1999Co-Authors: Ji-liang Gao, Eric J. Lee, Philip M MurphyAbstract:N-Formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific Receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N-Formylpeptide Receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. Here we test this hypothesis in mice lacking the high affinity N-Formylpeptide Receptor (FPR), created by targeted gene disruption. FPR �� � mice developed normally, but had increased susceptibility to challenge with Listeria monocytogenes, as measured by increased mortality compared with wild-type littermates. FPR �� � mice also had increased bacterial load in spleen and liver 2 d after infection, which is before development of a specific cellular immune response, suggesting a defect in innate immunity. Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N-Formylpeptide fMLF (formyl-methionyl-leucyl-phenylalanine) were both absent in FPR �� � mice. These results indicate that FPR functions in antibacterial host defense in vivo. Key words: chemotaxis • Listeria • inflammation • chemoattractant • neutrophi
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A high potency non-formylated peptide agonist for the phagocyte N-Formylpeptide chemotactic Receptor
1994Co-Authors: Ji-liang Gao, Natesa Muthukumaraswamy, Richard J. Freer, Elmer L. Becker, Philip M MurphyAbstract:Analysis of synthetic tri- and tetrapeptides has previously indicated that N-formylation is required for high biological activity when they react with the phagocyte N-Formylpeptide Receptor, suggesting that the natural ligand for the Receptor is from bacterial and/or mitochondrial sources. To explore this requirement further, we synthesized the pentapeptide methionyl-norleucyl-leucyl-phenylalanylphenylalanine (MNIeLFF) and studied the effects of different NH2-terminal modifications on its activity. N-formyl-MNleLFF induced transient alterations of [Ca2+]i and superoxide production in human neutrophils with 10- and 100-fold greater potency, respectively, than the prototype N-Formylpeptide, N-formylmethionyl-leucyl-phenylalanine (fMLF). Surprisingly, N-acetyl-MNleLFF was as potent as N-formyl-MNleLFF. Moreover, the unacylated counterpart H-MNleLFF was also highly active, having an ECs0 for calcium mobilization of 10 riM, and for respiratory burst activation of 100 nM. All three pentapeptides could completely desensitize calcium transients elicited by stimulation of neutrophils with fMLF, whereas the neutrophil chemoattractants CSa and interleukin 8 only weakly affected fMLF-induced transients, suggesting that they activate neutrophils via the same Receptor as fMLF. Finally, all three pentapeptides activated the recombinant human N-Formylpeptide Receptor expressed in frog oocytes, but did not effectively activate relate
Wanghua Gong - One of the best experts on this subject based on the ideXlab platform.
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Formylpeptide Receptor FPR and the Rapid Growth of Malignant Human Gliomas
2015Co-Authors: Ye Zhou, Wanghua Gong, Xiuwu Bian, Xia Zhang, Lihua Wang, Pablo Iribarren, Rosalba Salcedo, O. Zack M. HowardAbstract:Background: The Formylpeptide Receptor (FPR) is a G-protein – coupled Receptor (GPCR) that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF). We previ-ously showed that selected human glioma cell lines also express functional FPR. We therefore investigated the relationship between FPR expression and the biologic behavior of glioma cells. Methods: Expression and function of FPR in the human glioblastoma cell line U-87 were examined by reverse transcription – polymerase chain reaction (RT-PCR) and chemotaxis assays, respectively. FPR protein expression was detected in specimens from 33 human primary gliomas by im-munohistochemistry. FPR short interfering (si) RNA was used to block FPR expression in U-87 cells. Cell proliferation was assessed by measuring DNA synthesis. Xenograft tumor for
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the Formylpeptide Receptor 2 fpr2 and its endogenous ligand cathelin related antimicrobial peptide cramp promote dendritic cell maturation
Journal of Biological Chemistry, 2014Co-Authors: Keqiang Chen, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Jiaqiang Huang, Yi Xiang, Qun Jiang, Ji Ming WangAbstract:Mouse Formylpeptide Receptor 2 (Fpr2) is a homologue of the human G-protein coupled chemoattractant Receptor FPR2, which interacts with pathogen and host-derived chemotactic agonists. Our previous studies revealed reduced allergic airway inflammation and immune responses in Fpr2-deficient (Fpr2(-/-)) mice in association with diminished dendritic cell (DC) recruitment into the airway and draining lymph nodes. These defects prompted us to investigate the potential changes in the differentiation and maturation of DCs caused by Fpr2 deficiency. Bone marrow monocytes from Fpr2(-/-) mouse mice incubated with GM-CSF and IL-4 in vitro showed normal expression of markers of immature DCs. However, upon stimulation with the TLR4 agonist LPS, Fpr2(-/-) mouse DCs failed to express normal levels of maturation markers with reduced production of IL-12 and diminished chemotaxis in response to the DC homing chemokine CCL21. Fpr2(-/-) DCs also failed to induce allogeneic T-cell proliferation in vitro, and their recruitment into the T-cell zones of the spleen was reduced after antigen immunization. The capacity of Fpr2 to sustain normal DC maturation was dependent on its interaction with an endogenous ligand CRAMP expressed by DCs, because neutralization of either Fpr2 or CRAMP inhibited DC maturation in response to LPS. We additionally observed that the presence of exogenous CRAMP in culture increased the sensitivity of WT mouse DCs to LPS stimulation. The importance of CRAMP for DC maturation was further demonstrated by the observations that DCs from CRAMP(-/-) mice expressed lower levels of costimulatory molecules and MHC II and exhibited poor chemotaxis in response to CCL21 after LPS stimulation. Our observations indicate a nonredundant role for Fpr2 and its agonist CRAMP in DC maturation in immune responses.
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50 Cellular & Molecular Immunology The Grape Component Resveratrol Interferes with the Function
2014Co-Authors: Hengyi Tao, Wanghua Gong, Ye Zhou, Xia Zhang, Pablo Iribarren, Yuqing Zhao, Ji Ming WangAbstract:Resveratrol (3, 5, 4'-trihydroxystilbene) (RV) is a constituent of grape seeds with anti-inflammatory and anti-oxidant activities. In this study, we examined the capacity of RV to modulate the function of G protein-coupled chemoattractant Receptors, which play important roles in inflammation and immune responses. RV, over a non-cytotoxic concentration range, inhibited chemotactic and calcium mobilization responses of phagocytic cells to selected chemoattractants. At low micromolar concentrations RV potently reduced superoxide anion production by phagocytic leukocytes in response to the bacterial chemotactic peptide fMLF, a high affinity ligand for Formylpeptide Receptor FPR, and Aβ42, an Alzheimer's disease-associated peptide and a ligand for the FPR variant FPRL1. In addition, RV reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and the activation of nuclear factor NF-κB induced by Formylpeptide Receptor agonists. These results suggest that the inhibition of the function of chemoattractant Receptors may contribute to the anti-inflammatory properties of RV. Thus, RV may be therapeutically promising for diseases in which activation of Formylpeptide Receptors contributes to the pathogenic processes. Cellular & Molecular Immunology. 2004
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signal relay by cc chemokine Receptor 2 ccr2 and Formylpeptide Receptor 2 fpr2 in the recruitment of monocyte derived dendritic cells in allergic airway inflammation
Journal of Biological Chemistry, 2013Co-Authors: Keqiang Chen, Mingyong Liu, Ying Liu, Chunyan Wang, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Ji Ming WangAbstract:Chemoattractant Receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine Receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in Formylpeptide Receptor Fpr2 (Fpr2−/−). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2−/− mice, in the inflamed airway of CRAMP−/− mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung. Background: Chemoattractant Receptor Fpr2 interacts with host-derived agonists and mediates leukocyte trafficking. Results: In the lung of allergic inflammation, chemokine Receptor CCR2 elicits accumulation of monocyte-derived DC in perivascular region, but Fpr2 is critical for cell trafficking to peribronchiolar area. Conclusion: CCR2 and Fpr2 sequentially guide DC trafficking in inflamed lung. Significance: DC trafficking is controlled by multiple chemoattractant Receptors, which are potential therapeutic targets.
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signal relay by cc chemokine Receptor 2 ccr2 and Formylpeptide Receptor 2 fpr2 in the recruitment of monocyte derived dendritic cells in allergic airway inflammation
Journal of Biological Chemistry, 2013Co-Authors: Keqiang Chen, Mingyong Liu, Ying Liu, Chunyan Wang, Teizo Yoshimura, Wanghua Gong, Lino Tessarollo, Ji Ming WangAbstract:Abstract Chemoattractant Receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine Receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in Formylpeptide Receptor Fpr2 (Fpr2−/−). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2−/− mice, in the inflamed airway of CRAMP−/− mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung.