The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Weisong Zhou - One of the best experts on this subject based on the ideXlab platform.
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Prostaglandin I2 signaling licenses treg suppressive function and prevents pathogenic reprogramming
Journal of Clinical Investigation, 2021Co-Authors: Allison E Norlander, Weisong Zhou, Shinji Toki, Jian Zhang, Melissa H Bloodworth, Kelli L Boyd, Vasiliy V Polosukhin, Jacquelineyvonne Cephus, Zachary J Ceneviva, Vivek D GandhiAbstract:T regulatory cells (Treg) restrain both the innate and adaptive immune systems to maintain homeostasis. Allergic airway inflammation, characterized by a type 2 (Th2) response that results from a breakdown of tolerance to innocuous environmental antigens, is negatively regulated by Treg. We previously reported that Prostaglandin I2 (PGI2) promoted immune tolerance in models of allergic inflammation; however, the effect of PGI2 on Treg function was not investigated. Treg from mice deficient in the PGI2 receptor IP (IP KO) had impaired suppressive capabilities during allergic airway inflammatory responses compared to mice with PGI2 signaling was intact. IP KO Treg had significantly enhanced expression of immunoglobulin-like transcript 3 (ILT3) compared to wild-type Treg, which may contribute to the impairment of the IP KO Treg's ability to suppress Th2 responses. Using fate-mapping mice, we reported that PGI2 signaling prevents Treg reprogramming toward a pathogenic phenotype. PGI2 analogs promoted the differentiation of naive T cells to Treg in both mice and humans via repression of β-catenin signaling. Finally, a missense variant in IP in humans was strongly associated with chronic obstructive asthma. Together, these data support that PGI2 signaling licenses Treg suppressive function and that PGI2 is a therapeutic target to enhance Treg function.
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Prostaglandin I2 suppresses proinflammatory chemokine expression cd4 t cell activation and stat6 independent allergic lung inflammation
Journal of Immunology, 2016Co-Authors: Weisong Zhou, Dawn C Newcomb, Kasia Goleniewska, Shinji Toki, Jian Zhang, Daniel E Dulek, Jacqueline Cephus, Robert D Collins, Mark Boothby, Stokes R PeeblesAbstract:Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. In this study, using the mouse model of OVA-induced allergic airway inflammation, we identified that PGI2 receptor (IP) signaling was critical for indomethacin-induced, STAT6-independent proallergic effects. We demonstrated that IP deficiency increased inflammatory cell infiltration, eosinophilia, and IL-5 and IL-13 expression in the lung in a STAT6-independent manner. The augmented STAT6-independent allergic inflammation correlated with enhanced primary immune responses to allergic sensitization and elevated production of multiple inflammatory chemokines (CCL11, CCL17, CCL22, and CXCL12) in the lung after allergen challenge. We also showed that the PGI2 analogue cicaprost inhibited CD4 T cell proliferation and IL-5 and IL-13 expression in vitro, and IP deficiency diminished the stimulatory effect of indomethacin on STAT6-independent IL-5 and IL-13 responses in vivo. The inhibitory effects of PGI2 and the IP signaling pathway on CD4 T cell activation, inflammatory chemokine production, and allergic sensitization and airway inflammation suggest that PGI2 and its analogue iloprost, both Food and Drug Administration-approved drugs, may be useful in treating allergic diseases and asthma. In addition, inhibiting PGI2 signaling by drugs that either block PGI2 production or restrain IP signaling may augment STAT6-independent pathways of allergic inflammation.
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Prostaglandin I2 signaling and inhibition of group 2 innate lymphoid cell responses
American Journal of Respiratory and Critical Care Medicine, 2015Co-Authors: Weisong Zhou, Dawn C Newcomb, Shinji Toki, Jian Zhang, Melissa H Bloodworth, Daniel E Dulek, Kasia Goleniewksa, Jacqueline Cephus, Matthew T Stier, Vasiliy PolosuhkinAbstract:Rationale: Group 2 innate lymphoid cells (ILC2s) robustly produce IL-5 and IL-13, cytokines central to the asthma phenotype; however, the effect of Prostaglandin (PG) I2 on ILC2 function is unknown.Objectives: To determine the effect of PGI2 on mouse and human ILC2 cytokine expression in vitro and the effect of endogenous PGI2 and the PGI2 analog cicaprost on lung ILC2s in vivo.Methods: Flow-sorted bone marrow ILC2s of wild-type (WT) and PGI2 receptor–deficient (IP−/−) mice were cultured with IL-33 and treated with the PGI2 analog cicaprost. WT and IP−/− mice were challenged intranasally with Alternaria alternata extract for 4 consecutive days to induce ILC2 responses, and these were quantified. Prior to A. alternata extract, challenged WT mice were treated with cicaprost. Human flow-sorted peripheral blood ILC2s were cultured with IL-33 and IL-2 and treated with the PGI2 analog cicaprost.Measurement and Main Results: We demonstrate that PGI2 inhibits IL-5 and IL-13 protein expression by IL-33–stimulated ...
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Prostaglandin I2 inhibits il 33 induced il 5 and il 13 production by human type 2 innate lymphoid cells
World Allergy Organization Journal, 2015Co-Authors: Weisong Zhou, Dawn C Newcomb, Kasia Goleniewska, Shinji Toki, Jian Zhang, Stokes R PeeblesAbstract:Background Group 2 innate lymphoid cells (ILC2) are characterized by their expression of cytokines including IL-5 and IL-13 in response to IL-33. ILC2 are critical in mediating influenza virus-induced airway hypersensitivity and are associated with allergic inflammation. However, the factors regulating human ILC2 (hILC2) cytokine responses are not fully defined. In this study, we tested the hypothesis that Prostaglandin I2 (PGI2), a lipid product formed in the cyclooxygenase (COX) pathway of arachidonic acid metabolism, suppresses IL-33-induced cytokine responses by hILC2.
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cyclooxygenase inhibition abrogates aeroallergen induced immune tolerance by suppressing Prostaglandin I2 receptor signaling
The Journal of Allergy and Clinical Immunology, 2014Co-Authors: Weisong Zhou, Dawn C Newcomb, Madison G Boswell, Kasia Goleniewska, Matthew T Lotz, Shinji Toki, Jian Zhang, Vasiliy V Polosukhin, Daniel E Dulek, Ginger L MilneAbstract:Background The prevalence of allergic diseases has doubled in developed countries in the past several decades. Cyclooxygenase (COX)-inhibiting drugs augmented allergic diseases in mice by increasing allergic sensitization and memory immune responses. However, whether COX inhibition can promote allergic airway diseases by inhibiting immune tolerance is not known. Objective To determine the role of the COX pathway and Prostaglandin I2 (PGI2) signaling through the PGI2 receptor (IP) in aeroallergen-induced immune tolerance. Methods Wild-type (WT) BALB/c mice and IP knockout mice were aerosolized with ovalbumin (OVA) to induce immune tolerance prior to immune sensitization with an intraperitoneal injection of OVA/alum. The COX inhibitor indomethacin or vehicle was administered in drinking water to inhibit enzyme activity during the sensitization phase. Two weeks after sensitization, the mice were challenged with OVA aerosols. Mouse bronchoalveolar lavage fluid was harvested for cell counts and TH2 cytokine measurements. Results WT mice treated with indomethacin had greater numbers of total cells, eosinophils, and lymphocytes, and increased IL-5 and IL-13 protein expression in BAL fluid compared to vehicle-treated mice. Similarly, IP knockout mice had augmented inflammation and TH2 cytokine responses compared to WT mice. In contrast, the PGI2 analog cicaprost attenuated the anti-tolerance effect of COX inhibition. Conclusion COX inhibition abrogated immune tolerance by suppressing PGI2 IP signaling, suggesting that PGI2 signaling promotes immune tolerance and that clinical use of COX-inhibiting drugs may increase the risk of developing allergic diseases.
John S Charnock - One of the best experts on this subject based on the ideXlab platform.
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differential effects of dietary fish oil on myocardial Prostaglandin I2 and thromboxane a2 production
American Journal of Physiology-heart and Circulatory Physiology, 1991Co-Authors: Mahinda Y Abeywardena, Peter L Mclennan, John S CharnockAbstract:Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil...
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differential effects of dietary fish oil on myocardial Prostaglandin I2 and thromboxane a2 production
American Journal of Physiology-heart and Circulatory Physiology, 1991Co-Authors: Mahinda Y Abeywardena, Peter L Mclennan, John S CharnockAbstract:Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil (SSO), or tuna fish oil (TFO). The polyunsaturated fatty acids (PUFA) of myocardial phospholipids demonstrated significant alterations as a result of the dietary (n-3) or (n-6) lipid supplementation. The reduction (P less than 0.05) in Prostaglandin (PG) I2 in PUFA diet-fed groups (SSO, 113.8 +/- 7.8; TFO, 87.9 +/- 8.2 compared with Ref, 153.9 +/- 7.4 pg/mg dry wt) seems to be due to the rate limitation of the endogenous substrate, because the addition of exogenous arachidonic acid (AA) has obliterated the dietary difference. However, AA did not increase the basal PGI2 production in the Ref or SF dietary groups, which differed from that for thromboxane (Tx) A2 where 2- to 5-fold stimulation was observed. It is suggested that there exists a preferential channeling mechanism to direct AA derived from phospholipase hydrolysis of membrane phospholipids toward PGI2 synthesis. Conversely, the bulk of the AA for TxA2 biosynthesis appears to be supplied by a cytosolic nonesterified fatty acid pool. The effective replacement of AA of this pool and a specific inhibition of TxA2 synthetase enzyme complex by the (n-3) PUFA of fish oil are offered as likely mechanisms for the greater inhibition of TxA2 compared with PGI2 production observed in the present and previous studies. The present data on myocardial eicosanoids correlate well with the beneficial qualities of (n-3) and (n-6) dietary PUFA on cardiac function that we have reported previously.
Stokes R Peebles - One of the best experts on this subject based on the ideXlab platform.
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Prostaglandin I2 and t regulatory cell function broader impacts
DNA and Cell Biology, 2021Co-Authors: Allison E Norlander, Stokes R PeeblesAbstract:T regulatory cells (Tregs) are an important member of the adaptive immune system and function to reduce and resolve inflammation. Prostaglandin I2 (PGI2) is a lipid mediator that has potent anti-in...
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Prostaglandin I2 suppresses proinflammatory chemokine expression cd4 t cell activation and stat6 independent allergic lung inflammation
Journal of Immunology, 2016Co-Authors: Weisong Zhou, Dawn C Newcomb, Kasia Goleniewska, Shinji Toki, Jian Zhang, Daniel E Dulek, Jacqueline Cephus, Robert D Collins, Mark Boothby, Stokes R PeeblesAbstract:Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. In this study, using the mouse model of OVA-induced allergic airway inflammation, we identified that PGI2 receptor (IP) signaling was critical for indomethacin-induced, STAT6-independent proallergic effects. We demonstrated that IP deficiency increased inflammatory cell infiltration, eosinophilia, and IL-5 and IL-13 expression in the lung in a STAT6-independent manner. The augmented STAT6-independent allergic inflammation correlated with enhanced primary immune responses to allergic sensitization and elevated production of multiple inflammatory chemokines (CCL11, CCL17, CCL22, and CXCL12) in the lung after allergen challenge. We also showed that the PGI2 analogue cicaprost inhibited CD4 T cell proliferation and IL-5 and IL-13 expression in vitro, and IP deficiency diminished the stimulatory effect of indomethacin on STAT6-independent IL-5 and IL-13 responses in vivo. The inhibitory effects of PGI2 and the IP signaling pathway on CD4 T cell activation, inflammatory chemokine production, and allergic sensitization and airway inflammation suggest that PGI2 and its analogue iloprost, both Food and Drug Administration-approved drugs, may be useful in treating allergic diseases and asthma. In addition, inhibiting PGI2 signaling by drugs that either block PGI2 production or restrain IP signaling may augment STAT6-independent pathways of allergic inflammation.
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Prostaglandin I2 inhibits il 33 induced il 5 and il 13 production by human type 2 innate lymphoid cells
World Allergy Organization Journal, 2015Co-Authors: Weisong Zhou, Dawn C Newcomb, Kasia Goleniewska, Shinji Toki, Jian Zhang, Stokes R PeeblesAbstract:Background Group 2 innate lymphoid cells (ILC2) are characterized by their expression of cytokines including IL-5 and IL-13 in response to IL-33. ILC2 are critical in mediating influenza virus-induced airway hypersensitivity and are associated with allergic inflammation. However, the factors regulating human ILC2 (hILC2) cytokine responses are not fully defined. In this study, we tested the hypothesis that Prostaglandin I2 (PGI2), a lipid product formed in the cyclooxygenase (COX) pathway of arachidonic acid metabolism, suppresses IL-33-induced cytokine responses by hILC2.
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Prostaglandin I2 analogs inhibit th1 and th2 effector cytokine production by cd4 t cells
Journal of Leukocyte Biology, 2007Co-Authors: Weisong Zhou, Garret A Fitzgerald, Kasia Goleniewska, Timothy S Blackwell, Jamye F Oneal, Margaret B Lucitt, Richard M Breyer, Stokes R PeeblesAbstract:An anti-inflammatory effect of PGI(2) has been suggested by increased inflammation in mice that are deficient in the PGI(2) receptor (IP) or in respiratory syncytial viral- or OVA-induced CD4 T cell-associated responses. To determine the mechanism of the anti-inflammatory effect, we hypothesized that PGI(2) analogs inhibit CD4 T cell effector cytokine production. To test this hypothesis, we activated purified CD4 T cells with anti-CD3 and anti-CD28 antibodies under Th1 and Th2 polarizing conditions for 4 days and restimulated the T cells with anti-CD3 in the presence of PGI(2) analogs for 2 days. We found that PGI(2) analogs (cicaprost and iloprost) inhibited the production of Th1 cytokines (IFN-gamma) and Th2 cytokines (IL-4, IL-10, and IL-13) in a dose-dependent pattern. The inhibitory effect was partially dependent on the IP receptor signaling and was correlated with elevated intracellular cAMP and down-regulated NF-kappaB activity. Pretreatment of the CD4 T cells with 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Rp-isomer, to inhibit a key signaling molecule in the cAMP pathway, protein kinase A (PKA), attenuated the suppressive effect of PGI(2) analogs significantly, suggesting that PKA, in part, mediates the inhibition of the cytokine production. These data indicate that PGI(2) analogs have an immune-suppressive effect on previously activated and differentiated CD4 T cells in vitro and suggest that PGI(2) may have a similar function in vivo.
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Prostaglandin I2 analogs inhibit proinflammatory cytokine production and t cell stimulatory function of dendritic cells
Journal of Immunology, 2007Co-Authors: Weisong Zhou, Garret A Fitzgerald, Mark W. Geraci, Kasia Goleniewska, Timothy S Blackwell, Jamye F Oneal, Koichi Hashimoto, Karine Egan, Stokes R PeeblesAbstract:Signaling through the PGI2 receptor (IP) has been shown to inhibit inflammatory responses in mouse models of respiratory syncytial viral infection and OVA-induced allergic responses. However, little is known about the cell types that mediate the anti-inflammatory function of PGI2. In this study, we determined that PGI2 analogs modulate dendritic cell (DC) cytokine production, maturation, and function. We report that PGI2 analogs (iloprost, cicaprost, treprostinil) differentially modulate the response of murine bone marrow-derived DC (BMDC) to LPS in an IP-dependent manner. The PGI2 analogs decreased BMDC production of proinflammatory cytokines (IL-12, TNF-α, IL-1α, IL-6) and chemokines (MIP-1α, MCP-1) and increased the production of the anti-inflammatory cytokine IL-10 by BMDCs. The modulatory effect was associated with IP-dependent up-regulation of intracellular cAMP and down-regulation of NF-κB activity. Iloprost and cicaprost also suppressed LPS-induced expression of CD86, CD40, and MHC class II molecules by BMDCs and inhibited the ability of BMDCs to stimulate Ag-specific CD4 T cell proliferation and production of IL-5 and IL-13. These findings suggest that PGI2 signaling through the IP may exert anti-inflammatory effects by acting on DC.
Shuh Narumiya - One of the best experts on this subject based on the ideXlab platform.
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Prostaglandin I2 suppresses the development of diet induced nonalcoholic steatohepatitis in mice
The FASEB Journal, 2017Co-Authors: Shima Kumei, Kohichi Yuhki, Fumiaki Kojima, Shuh Narumiya, Hitoshi Kashiwagi, Yoshitaka Imamichi, Toshikatsu Okumura, Fumitaka UshikubiAbstract:Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome. Although the Prostaglandin (PG)I2 receptor IP is expressed broadly in the liver, the role of PGI2-IP signaling in the development of NASH remains to be determined. Here, we investigated the role of the PGI2-IP system in the development of steatohepatitis using mice lacking the PGI2 receptor IP [IP-knockout (IP-KO) mice] and beraprost (BPS), a specific IP agonist. IP-KO and wild-type (WT) mice were fed a methionine- and choline-deficient diet (MCDD) for 2, 5, or 10 wk. BPS was administered orally to mice every day during the experimental periods. The effect of BPS on the expression of chemokine and inflammatory cytokines was examined also in cultured Kupffer cells. WT mice fed MCDD developed steatohepatitis at 10 wk. IP-KO mice developed steatohepatitis at 5 wk with augmented histologic derangements accompanied by increased hepatic monocyte chemoattractant protein-1 (MCP-1) and TNF-α concentrations. After 10 wk of MCDD, IP-KO mice had greater hepatic iron deposition with prominent oxidative stress, resulting in hepatocyte damage. In WT mice, BPS improved histologic and biochemical parameters of steatohepatitis, accompanied by reduced hepatic concentration of MCP-1 and TNF-α. Accordingly, BPS suppressed the LPS-stimulated Mcp-1 and Tnf-α mRNA expression in cultured Kupffer cells prepared from WT mice. PGI2-IP signaling plays a crucial role in the development and progression of steatohepatitis by modulating the inflammatory response, leading to augmented oxidative stress. We suggest that the PGI2-IP system is an attractive therapeutic target for treating patients with NASH.-Kumei, S., Yuhki, K.-I., Kojima, F., Kashiwagi, H., Imamichi, Y., Okumura, T., Narumiya, S., Ushikubi, F. Prostaglandin I2 suppresses the development of diet-induced nonalcoholic steatohepatitis in mice.
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neuroprotective properties of Prostaglandin I2 ip receptor in focal cerebral ischemia
Neuroscience, 2010Co-Authors: Sofiyan Saleem, Shuh Narumiya, Zahoor A Shah, Toshihiko Maruyama, Sylvain DoreAbstract:Abstract We and others have identified that inhibition of cyclooxygenase might not be the optimal approach to limiting brain damage after stroke. Now we are investigating the unique properties of the various Prostaglandin receptors to determine whether blocking those that mediate toxicity or stimulating those that reduce toxicity will improve neurological outcomes. Here, we determined the respective contribution of the Prostaglandin I 2 (PGI 2 ) receptor in transient middle cerebral artery (MCA) occlusion ( t MCAO) and permanent MCAO ( p MCAO) preclinical stroke models by using male wildtype (WT) and IP receptor knockout (IP −/− ) C57Bl/6 mice. In addition, we investigated the putative preventive and therapeutic effects of the IP receptor agonist beraprost. The infarct volumes and neurological deficit scores (NDS) were significantly greater in IP −/− than in WT mice after both t MCAO and p MCAO. Interestingly, beraprost pretreatment (50 or 100 μg/kg p.o.) 30 min before t MCAO and post-treatment (100 μg/kg p.o.) at 2 or 4.5 h of reperfusion significantly reduced the neurological deficit score and infarct volume in WT mice. Post-treatment with beraprost (100 μg/kg p.o.) 4.5 h after p MCAO also significantly decreased neurological deficits and infarct volume in WT mice. Together, these novel findings suggest for the first time that PGI 2 IP receptor activation can attenuate anatomical and functional damage following ischemic stroke.
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Prostaglandin I2 ip signaling promotes th1 differentiation in a mouse model of contact hypersensitivity
Journal of Immunology, 2010Co-Authors: Saeko Nakajima, Tetsuya Honda, Daiji Sakata, Gyohei Egawa, Hideaki Tanizaki, Atsushi Otsuka, Catharina Sagita Moniaga, Takeshi Watanabe, Yoshiki Miyachi, Shuh NarumiyaAbstract:PGI(2), which exerts its actions via its specific Gs-coupled I prostanoid receptor (IP), is known to be present in the lymph nodes, but its roles in acquired cutaneous immune responses remain unclear. To investigate the role of PGI(2)-IP signaling in cutaneous immune responses, we applied IP-deficient (Ptgir(-/-)) mice to contact hypersensitivity as a model of acquired immune response and found that Ptgir(-/-) mice exhibited a significantly decreased contact hypersensitivity response. Lymph node cells from sensitized Ptgir(-/-) mice exhibited decreased IFN-gamma production and a smaller T-bet(+) subset compared with control mice. PGI synthase and IP expression were detected in dendritic cells and T cells, respectively, by quantitative real-time PCR analysis, suggesting that PGI(2) produced by dendritic cells acts on IP in T cells. In fact, in vitro Th1 differentiation was enhanced by an IP agonist, and this enhancement was nullified by protein kinase A inhibitor. These results suggest that PGI(2)-IP signaling promotes Th1 differentiation through a cAMP-protein kinase A pathway and thereby initiates acquired cutaneous immune responses.
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Prostaglandin I2 plays a key role in zymosan induced mouse pleurisy
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Kohichi Yuhki, Fumitaka Ushikubi, Hiroaki Naraba, Akinori Ueno, Hirotsugu Kato, Fumiaki Kojima, Shuh Narumiya, Yukihiko Sugimoto, Misao Matsushita, Sachiko OhishiAbstract:Zymosan, the cell wall of Saccharomyces cerevisiae , induces innate immune responses involving prostanoid production and complement activation. However, the roles of prostanoids in zymosan-induced inflammation and their interaction with the complement system remain to be determined. To clarify these issues, we examined zymosan-induced pleurisy in mice lacking receptors for Prostaglandin (PG) E2 (EP–/– mice) or PGI2 (IP–/– mice). Zymosan-induced exudate formation was significantly reduced in IP–/– mice compared with wild-type (WT) mice, whereas none of the EP–/– mice (EP1–/–, EP2–/–, EP3–/–, and EP1–/–4 mice) showed any significant difference from WT mice. Furthermore, indomethacin, an inhibitor of prostanoid biosynthesis, suppressed exudate formation in WT mice to almost the same level as that of IP–/– mice. Accordingly, significant production of PGI2 in the pleural cavity, suggested to be cyclooxygenase-2-dependent, was observed after zymosan injection. Complement activation in the pleural cavity after zymosan injection was confirmed, and preinjection of cobra venom factor (CVF), to deplete blood complement C3, was significantly suppressed after zymosan-induced exudate formation in WT mice. Simultaneous treatment with indomethacin and CVF further suppressed exudate formation in WT mice compared with each treatment alone. Because, some degree of exudate formation was still observed, other factor(s) seem to be involved. However, platelet-activating factor, a promising candidate as one such factor, was not involved in zymosan-induced exudate formation. These results clearly indicate that the PGI2-IP system together with the complement system plays a key role in exudate formation in zymosan-induced pleurisy.
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role of Prostaglandin I2 in airway remodeling induced by repeated allergen challenge in mice
American Journal of Respiratory Cell and Molecular Biology, 2003Co-Authors: Koichi Nagao, Shuh Narumiya, Hiroyuki Tanaka, Masato Komai, Taisei Masuda, Hiroichi NagaiAbstract:Recently, we demonstrated that Prostaglandin (PG)I2 has a regulatory role in allergic responses through the receptor, IP; however, the role of PGI2 in airway remodeling associated with chronic airway inflammation has not been elucidated. In the present study, we examined the role of PGI2 in allergen-induced airway remodeling using IP gene–deficient mice. Mice were sensitized to ovalbumin (OVA) with alum, and exposed daily for 3 wk to aerosolized OVA. Twenty-four hours after the final antigen inhalation, bronchoalveolar lavage, biochemical, and histopathologic examinations were performed. In wild-type mice, prolonged allergen exposure in sensitized animals induced the increases in the numbers of inflammatory leukocytes (including eosinophils and lymphocytes), levels of T helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13), levels of OVA-specific immunoglobulin (Ig)E and IgG1 in serum, and amount of hydroxyproline in the right lungs associated with transforming growth factor-β1 levels in bro...
Mahinda Y Abeywardena - One of the best experts on this subject based on the ideXlab platform.
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differential effects of dietary fish oil on myocardial Prostaglandin I2 and thromboxane a2 production
American Journal of Physiology-heart and Circulatory Physiology, 1991Co-Authors: Mahinda Y Abeywardena, Peter L Mclennan, John S CharnockAbstract:Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil...
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differential effects of dietary fish oil on myocardial Prostaglandin I2 and thromboxane a2 production
American Journal of Physiology-heart and Circulatory Physiology, 1991Co-Authors: Mahinda Y Abeywardena, Peter L Mclennan, John S CharnockAbstract:Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil (SSO), or tuna fish oil (TFO). The polyunsaturated fatty acids (PUFA) of myocardial phospholipids demonstrated significant alterations as a result of the dietary (n-3) or (n-6) lipid supplementation. The reduction (P less than 0.05) in Prostaglandin (PG) I2 in PUFA diet-fed groups (SSO, 113.8 +/- 7.8; TFO, 87.9 +/- 8.2 compared with Ref, 153.9 +/- 7.4 pg/mg dry wt) seems to be due to the rate limitation of the endogenous substrate, because the addition of exogenous arachidonic acid (AA) has obliterated the dietary difference. However, AA did not increase the basal PGI2 production in the Ref or SF dietary groups, which differed from that for thromboxane (Tx) A2 where 2- to 5-fold stimulation was observed. It is suggested that there exists a preferential channeling mechanism to direct AA derived from phospholipase hydrolysis of membrane phospholipids toward PGI2 synthesis. Conversely, the bulk of the AA for TxA2 biosynthesis appears to be supplied by a cytosolic nonesterified fatty acid pool. The effective replacement of AA of this pool and a specific inhibition of TxA2 synthetase enzyme complex by the (n-3) PUFA of fish oil are offered as likely mechanisms for the greater inhibition of TxA2 compared with PGI2 production observed in the present and previous studies. The present data on myocardial eicosanoids correlate well with the beneficial qualities of (n-3) and (n-6) dietary PUFA on cardiac function that we have reported previously.
