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10.1186/s12891-017-1819-3 http://scihub22266oqcxt.onion/10.1186/s12891-017-1819-3 C5691865!5691865 !29145862     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29145862 &cmd=llinks): Failed to open stream: HTTP request failed! 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L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-regulating Interleukin-17 and monocyte-chemoattractant protein-1 levels |pdf=|usr=}}{{29145862 }} gab.com Text L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-regulating Interleukin-17 and monocyte-chemoattractant protein-1 levels JO: BMC Musculoskelet Disord http://www.kidney.de/pget.php?&tw=1&pmid=29145862 #FOAvip BACKGROUND: To investigate the effects and potential mechanism of L161982 (a kind of EP4 antagonist) on the collagen-induced arthritis (CIA) mice model. METHODS: The CIA mice model were first established by immunizing with Chicken Type II Collagen on DBA/1 mice. The CIA groups were administered once a day for 2 weeks with either 5 mg/kg L161982 by intraperitoneal injections (IP), 200 U celecoxib by intragastrical injections, or 100 ?l PBS (IP). At the end of the study, total arthritis score and histopathologic examination were assessed to determine CIA severity. The plasma and tissue expressions of IL-17 and monocyte chemoattractant protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA) and Immunohistochemical staining (IHC) respectively; The number of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) determined as a proportion of total CD4(+) cells in the lymph nodes and spleen. We also tested the proliferation of isolated Tregs and the ratio of Th17 polarization of Naïve T cells under the treatment of L161982 by BrdU assay and flow cytometry respectively. RESULTS: CIA mice treated with L161982 showed reduced arthritis scores, joint swellings, cracked cartilage surface, and less hyperplasia in the connective tissue of the articular cavity. Plasma and tissue IL-17 and MCP-1 decreased, while the proportion of Treg cells is increased both in the spleen and lymph nodes of CIA mice. Otherwise, L161982 have no direct effect on Tregs proliferation; a decreased tendency of Th17 polarization in vitro were observed in L161982-treated naïve T cells. CONCLUSION: Although less effective than Celecoxib, L161982 also resulted in a reduction of ankle joint inflammation in CIA mice. L161982 reduces the RA severity in CIA mice through inhibition of IL-17 and MCP-1, increasing Treg cells, and reducing inflammation. The mechanism of the reduction of IL-17 in plasma or tissue after administration of L161982 might be potentially derived from the suppression of CD4(+) T cells differentiation into Th-17 cells. Twit Text FOAVip L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-regulating Interleukin-17 and monocyte-chemoattractant protein-1 levels ????BMC Musculoskelet Disord http://www.kidney.de/pget.php?&tw=1&pmid=29145862 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29145862 #FOAvip English Wikipedia <ref>{{Cite pmid|29145862 }}</ref> L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-regulating Interleukin-17 and monocyte-chemoattractant protein-1 levels #MMPMID29145862 Chen L ; Wu X ; Zhong J ; Li D BMC Musculoskelet Disord 2017[Nov]; 18 (1 ): 462 PMID29145862 show ga BACKGROUND: To investigate the effects and potential mechanism of L161982 (a kind of EP4 antagonist) on the collagen-induced arthritis (CIA) mice model. METHODS: The CIA mice model were first established by immunizing with Chicken Type II Collagen on DBA/1 mice. The CIA groups were administered once a day for 2 weeks with either 5 mg/kg L161982 by intraperitoneal injections (IP), 200 U celecoxib by intragastrical injections, or 100 ?l PBS (IP). At the end of the study, total arthritis score and histopathologic examination were assessed to determine CIA severity. The plasma and tissue expressions of IL-17 and monocyte chemoattractant protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA) and Immunohistochemical staining (IHC) respectively; The number of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) determined as a proportion of total CD4(+) cells in the lymph nodes and spleen. We also tested the proliferation of isolated Tregs and the ratio of Th17 polarization of Naïve T cells under the treatment of L161982 by BrdU assay and flow cytometry respectively. RESULTS: CIA mice treated with L161982 showed reduced arthritis scores, joint swellings, cracked cartilage surface, and less hyperplasia in the connective tissue of the articular cavity. Plasma and tissue IL-17 and MCP-1 decreased, while the proportion of Treg cells is increased both in the spleen and lymph nodes of CIA mice. Otherwise, L161982 have no direct effect on Tregs proliferation; a decreased tendency of Th17 polarization in vitro were observed in L161982-treated naïve T cells. CONCLUSION: Although less effective than Celecoxib, L161982 also resulted in a reduction of ankle joint inflammation in CIA mice. L161982 reduces the RA severity in CIA mice through inhibition of IL-17 and MCP-1, increasing Treg cells, and reducing inflammation. The mechanism of the reduction of IL-17 in plasma or tissue after administration of L161982 might be potentially derived from the suppression of CD4(+) T cells differentiation into Th-17 cells. |Animals [MESH] |Ankle Joint/drug effects/pathology [MESH] |Arthritis, Experimental/blood/*drug therapy/immunology [MESH] |Arthritis, Rheumatoid/blood/*drug therapy/immunology [MESH] |Celecoxib/pharmacology/therapeutic use [MESH] |Cell Differentiation/drug effects/immunology [MESH] |Cell Proliferation/drug effects [MESH] |Chemokine CCL2/blood/immunology/*metabolism [MESH] |Collagen Type II/immunology [MESH] |Cyclooxygenase 2 Inhibitors/pharmacology/therapeutic use [MESH] |Dinoprostone/metabolism [MESH] |Down-Regulation [MESH] |Female [MESH] |Humans [MESH] |Injections, Intraperitoneal [MESH] |Interleukin-17/blood/immunology/*metabolism [MESH] |Mice [MESH] |Mice, Inbred DBA [MESH] |Receptors, Prostaglandin E, EP4 Subtype/antagonists & inhibitors/metabolism [MESH] |Severity of Illness Index [MESH] |Signal Transduction/drug effects/immunology [MESH] |T-Lymphocytes, Regulatory/*drug effects/immunology [MESH] |Th17 Cells/immunology [MESH] |Thiophenes/*pharmacology/therapeutic use [MESH]L161982 alleviates collagen-induced arthritis in mice by increasing Tr(epmc).pdf DeepDyve Pubget Overpricing