The Experts below are selected from a list of 38436 Experts worldwide ranked by ideXlab platform
Suofu Qin - One of the best experts on this subject based on the ideXlab platform.
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Blockade of MerTK Activation by AMPK Inhibits RPE Cell Phagocytosis.
Advances in experimental medicine and biology, 2015Co-Authors: Suofu QinAbstract:Timely removal of shed photoreceptor outer segments by retinal pigment epithelial Cells (RPE) plays a key role in biological renewal of these highly peroxidizable structures and in maintenance of retina health. How environmental stress cause RPE Cell dysfunction is undefined however. AMP-activated protein kinase (AMPK), a heterotrimer of a catalytic α subunit and regulatory β and γ subunits, maintains energy homeostasis by limiting energy utilization and/or promoting energy production when energy supply is compromised. Intriguingly, AMPK has been shown to be important in functions of RPE Cells. In this mini-review, the role and mechanisms of AMPK in controlling RPE Cell Phagocytosis are discussed.
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Roles of αvβ5, FAK and MerTK in oxidative stress inhibition of RPE Cell Phagocytosis.
Experimental eye research, 2011Co-Authors: Suofu Qin, Gerard A. RodriguesAbstract:Abstract Efficient Phagocytosis of photoreceptor outer segments (POS) by retinal pigment epithelial Cells (RPE) plays a key role in biological renewal of these highly peroxidizable structures and in maintenance of retina health. Here, we used an in vitro RPE Cell Phagocytosis assay to investigate how sub-lethal oxidative stress modifies the key components of the Cell phagocytic machinery leading to severe impairment of Phagocytosis. Sub-lethal oxidative treatment, induced by hydrogen peroxide (H 2 O 2 ), significantly inhibited binding and uptake of POS by RPE Cells. However, sub-lethal oxidative stress did not affect Cell surface expression of αvβ5 or RPE Cell adhesion to αvβ5. Similarly, the enzymatic activity of mature cathepsin D was not altered upon challenge by oxidative stress. In contrast, studies of signaling molecules in the RPE Cell phagocytic machinery revealed that sub-lethal oxidative stress inhibits POS-induced activation of FAK and MerTK. Our data demonstrate that sub-lethal oxidative treatment with H 2 O 2 inhibits phagocytic activity of ARPE-19 Cells, in part by inhibiting FAK and MerTK.
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Roles for AMP-activated protein kinase in RPE Cell function.
Advances in experimental medicine and biology, 2011Co-Authors: Suofu QinAbstract:AMP-activated protein kinase (AMPK) is a heterotrimer, comprising a catalytic α subunit and regulatory β and γ subunits, that senses Cellular energy levels. When energy supply is compromised, activated AMPK limits energy utilization and promotes energy production to ensue Cell survival. Intriguingly, recent findings show that AMPK is important in functions that go beyond the maintenance of energy homeostasis. In this mini-review, the role of AMPK in controlling retinal pigment epithelium Cell Phagocytosis, permeability, immune response, and survival under oxidative stress is discussed.
Irshad H Chaudry - One of the best experts on this subject based on the ideXlab platform.
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mechanism of the salutary effects of estrogen on kupffer Cell phagocytic capacity following trauma hemorrhage pivotal role of akt activation
Journal of Immunology, 2009Co-Authors: Chi Hsun Hsieh, Mashkoor A Choudhry, Martin G Schwacha, Kirby I Bland, Eike A Nickel, Jianguo Chen, Irshad H ChaudryAbstract:Kupffer Cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer Cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer Cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and Cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer Cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-κB and ATP content of Kupffer Cells were also determined. Trauma-hemorrhage suppressed Kupffer Cell Phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-κB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-α, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer Cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer Cell Phagocytosis.
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Trauma-Hemorrhage and Hypoxia Differentially Influence Kupffer Cell Phagocytic Capacity: Role of Hypoxia-Inducible-Factor-1α and Phosphoinositide 3-Kinase/Akt Activation
Annals of surgery, 2009Co-Authors: Chi Hsun Hsieh, Martin G Schwacha, Kirby I Bland, Eike A Nickel, Jun-te Hsu, Irshad H ChaudryAbstract:Objective We investigated whether Kupffer Cell Phagocytosis is differentially regulated following hypoxia (by breathing hypoxic gas) and trauma-hemorrhage. We hypothesized that the differences might result from a differential activation of hypoxia-inducible factor (HIF)-1α and phosphoinositide 3-kinase (PI3K)/Akt pathway under those conditions.
Shigetada Kawabata - One of the best experts on this subject based on the ideXlab platform.
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Streptococcus pneumoniae Evades Host Cell Phagocytosis and Limits Host Mortality Through Its Cell Wall Anchoring Protein PfbA
Frontiers in cellular and infection microbiology, 2019Co-Authors: Masaya Yamaguchi, Yujiro Hirose, Moe Takemura, Masayuki Ono, Tomoko Sumitomo, Masanobu Nakata, Yutaka Terao, Shigetada KawabataAbstract:Streptococcus pneumoniae is a Gram-positive bacterium belonging to the oral streptococcus species, mitis group. This pathogen is a leading cause of community-acquired pneumonia, which often evades host immunity and causes systemic diseases, such as sepsis and meningitis. Previously, we reported that PfbA is a β-helical Cell surface protein contributing to pneumococcal adhesion to and invasion of human epithelial Cells in addition to its survival in blood. In the present study, we investigated the role of PfbA in pneumococcal pathogenesis. Phylogenetic analysis indicated that the pfbA gene is highly conserved in S. pneumoniae and Streptococcus pseudopneumoniae within the mitis group. Our in vitro assays showed that PfbA inhibits neutrophil Phagocytosis, leading to pneumococcal survival. We found that PfbA activates NF-κB through TLR2, but not TLR4. In addition, TLR2/4 inhibitor peptide treatment of neutrophils enhanced the survival of the S. pneumoniae ΔpfbA strain as compared to a control peptide treatment, whereas the treatment did not affect survival of a wild-type strain. In a mouse pneumonia model, the host mortality and level of TNF-α in bronchoalveolar lavage fluid were comparable between wild-type and ΔpfbA-infected mice, while deletion of pfbA decreased the bacterial burden in bronchoalveolar lavage fluid. In a mouse sepsis model, the ΔpfbA strain demonstrated significantly increased host mortality and TNF-α levels in plasma, but showed reduced bacterial burden in lung and liver. These results indicate that PfbA may contribute to the success of S. pneumoniae species by inhibiting host Cell Phagocytosis, excess inflammation, and mortality by interacting with TLR2.
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Streptococcus pneumoniae evades host Cell Phagocytosis and limits host mortality through its Cell wall anchoring protein PfbA
2019Co-Authors: Masaya Yamaguchi, Yujiro Hirose, Moe Takemura, Masayuki Ono, Tomoko Sumitomo, Masanobu Nakata, Yutaka Terao, Shigetada KawabataAbstract:Streptococcus pneumoniae is a Gram-positive bacterium belonging to the oral streptococcus species, mitis group. This pathogen is a leading cause of community-acquired pneumonia, which often evades host immunity and causes systemic diseases, such as sepsis and meningitis. Previously, we reported that PfbA is a {beta}-helical Cell surface protein contributing to pneumococcal adhesion to and invasion of human epithelial Cells in addition to its survival in blood. In the present study, we investigated the role of PfbA in pneumococcal pathogenesis. Phylogenetic analysis indicated that the pfbA gene is specific to S. pneumoniae within the mitis group. Our in vitro assays showed that PfbA inhibits neutrophil Phagocytosis, leading to pneumococcal survival. We found that PfbA activates NF-{kappa}B through TLR2, but not TLR4. In addition, TLR2/4 inhibitor peptide treatment of neutrophils enhanced the survival of the S. pneumoniae {Delta}pfbA strain as compared to a control peptide treatment, whereas the treatment did not affect survival of a wild-type strain. In a mouse pneumonia model, the host mortality and level of TNF- in bronchoalveolar lavage fluid were comparable between wild-type and {Delta}pfbA-infected mice, while deletion of pfbA increased the bacterial burden in bronchoalveolar lavage fluid. In a mouse sepsis model, the {Delta}pfbA strain demonstrated significantly increased host mortality and TNF- levels in plasma, but showed reduced bacterial burden in lung and liver. These results indicate that PfbA may contribute to the success of S. pneumoniae species by inhibiting host Cell Phagocytosis, excess inflammation, and mortality.nnImportanceStreptococcus pneumoniae is often isolated from the nasopharynx of healthy children, but the bacterium is also a leading cause of pneumonia, meningitis, and sepsis. In this study, we focused on the role of a Cell wall anchoring protein, PfbA, in the pathogenesis of S. pneumoniae-related disease. We found that PfbA is a pneumococcus-specific anti-phagocytic factor that functions as a TLR2 ligand, indicating that PfbA may represent a pneumococcal-specific therapeutic target. However, a mouse pneumonia model revealed that PfbA deficiency reduced the bacterial burden, but did not decrease host mortality. Furthermore, in a mouse sepsis model, PfbA deficiency increased host mortality. These results suggest that S. pneumoniae optimizes reproduction by regulating host mortality through PfbA; therefore, PfbA inhibition would not be an effective strategy for combatting pneumococcal infection. Our findings underscore the challenges involved in drug development for a bacterium harboring both commensal and pathogenic states.
Eunee Koh - One of the best experts on this subject based on the ideXlab platform.
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nanocage therapeutics prevailing Phagocytosis and immunogenic Cell death awakens immunity against cancer
Advanced Materials, 2018Co-Authors: Eunee Koh, Eun Jung Lee, Gi Hoon Nam, Na Kyeong Lee, Minwoo KihAbstract:A growing appreciation of the relationship between the immune system and the tumorigenesis has led to the development of strategies aimed at "re-editing" the immune system to kill tumors. Here, a novel tactic is reported for overcoming the activation-energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system. This nature-derived nanocage not only efficiently presents ligands that enhance cancer Cell Phagocytosis, but also delivers drugs that induce immunogenic cancer Cell death. The designed nanocage-therapeutics induce the release of neoantigens and danger signals in dying tumor Cells, and leads to enhancement of tumor Cell Phagocytosis and cross-priming of tumor specific T Cells by neoantigen peptide-loaded antigen-presenting Cells. Potent inhibition of tumor growth and complete eradication of tumors is observed through systemic tumor-specific T Cell responses in tumor draining lymph nodes and the spleen and further, infiltration of CD8+ T Cells into the tumor site. Remarkably, after removal of the primary tumor, all mice treated with this nanocage-therapeutics are protected against subsequent challenge with the same tumor Cells, suggesting development of lasting, tumor-specific responses. This designed nanocage-therapeutics "awakens" the host's immune system and provokes a durable systemic immune response against cancer.
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Exosome-SIRPα, a CD47 blockade increases cancer Cell Phagocytosis
Biomaterials, 2017Co-Authors: Eunee Koh, Eun Jung Lee, Gi Hoon Nam, Yeonsun Hong, Eunji Cho, Yoosoo Yang, In-san KimAbstract:CD47, a “don't eat me” signal, is over-expressed on the surface of most tumors that interacts with signal regulatory protein α (SIRPα) on phagocytic Cells. By engaging SIRPα, CD47 limits the ability of macrophages to engulf tumor Cells, which acts as a major phagocytic barrier. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRPα. These exosomes harboring SIRPα variants (SIRPα-exosomes) were sufficient to induce remarkably augmented tumor Phagocytosis, lead to prime effective anti-tumor T Cell response. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRPα on macrophage, nature-derived exosomes could be appreciable platform to antagonize CD47. Disruption of CD47-SIRPα interaction by SIRPα-exosomes leads to an increase in Cells being engulfed by macrophages and a concomitant inhibition of tumor growth in tumor-bearing mice. Moreover, SIRPα-exosomes therapy promotes an intensive T Cell infiltration in syngeneic mouse models of cancer, raising the possibility of CD47-targeted therapies to unleash both an innate and adaptive anti-tumor response. Note that very small amount of exosomal SIRPα proteins could effectively lead to phagocytic elimination of tumor Cells both in vitro and in vivo. Our results suggest that superlative exosome-based platform has broad potential to maximize the therapeutic efficacy of membrane-associated protein therapeutics.
Chi Hsun Hsieh - One of the best experts on this subject based on the ideXlab platform.
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mechanism of the salutary effects of estrogen on kupffer Cell phagocytic capacity following trauma hemorrhage pivotal role of akt activation
Journal of Immunology, 2009Co-Authors: Chi Hsun Hsieh, Mashkoor A Choudhry, Martin G Schwacha, Kirby I Bland, Eike A Nickel, Jianguo Chen, Irshad H ChaudryAbstract:Kupffer Cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer Cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer Cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and Cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer Cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-κB and ATP content of Kupffer Cells were also determined. Trauma-hemorrhage suppressed Kupffer Cell Phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-κB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-α, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer Cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer Cell Phagocytosis.
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Trauma-Hemorrhage and Hypoxia Differentially Influence Kupffer Cell Phagocytic Capacity: Role of Hypoxia-Inducible-Factor-1α and Phosphoinositide 3-Kinase/Akt Activation
Annals of surgery, 2009Co-Authors: Chi Hsun Hsieh, Martin G Schwacha, Kirby I Bland, Eike A Nickel, Jun-te Hsu, Irshad H ChaudryAbstract:Objective We investigated whether Kupffer Cell Phagocytosis is differentially regulated following hypoxia (by breathing hypoxic gas) and trauma-hemorrhage. We hypothesized that the differences might result from a differential activation of hypoxia-inducible factor (HIF)-1α and phosphoinositide 3-kinase (PI3K)/Akt pathway under those conditions.