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10.1073/pnas.1415762111 http://scihub22266oqcxt.onion/10.1073/pnas.1415762111 C4217397!4217397 !25316791     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25316791 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Proc+Natl+Acad+Sci+U+S+A 2014 ; 111 (43 ): E4658-67 Nephropedia Template TP {{tp|p=25316791 |t=2014. Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis |pdf=|usr=}}{{25316791 }} gab.com Text Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=25316791 #FOAvip Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with inflammatory bowel diseases (IBDs). Here we show that Tpl2 may exert a dominant homeostatic rather than inflammatory function in the intestine mediated specifically by subepithelial intestinal myofibroblasts (IMFs). Mice with complete or IMF-specific Tpl2 ablation are highly susceptible to epithelial injury-induced colitis showing impaired compensatory proliferation in crypts and extensive ulcerations without significant changes in inflammatory responses. Following epithelial injury, IMFs sense innate or inflammatory signals and activate, via Tpl2, the cyclooxygenase-2 (Cox-2)-prostaglandin E2 (PGE2) pathway, which we show here to be essential for the epithelial homeostatic response. Exogenous PGE2 administration rescues mice with complete or IMF-specific Tpl2 ablation from defects in crypt function and susceptibility to colitis. We also show that Tpl2 expression is decreased in IMFs isolated from the inflamed ileum of IBD patients indicating that Tpl2 function in IMFs may be highly relevant to human disease. The IMF-mediated mechanism we propose also involves the IBD-associated genes IL1R1, MAPK1, and the PGE2 receptor-encoding PTGER4. Our results establish a previously unidentified myofibroblast-specific innate pathway that regulates intestinal homeostasis and may underlie IBD susceptibility in humans. Twit Text FOAVip Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=25316791 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25316791 #FOAvip English Wikipedia <ref>{{Cite pmid|25316791 }}</ref> Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis #MMPMID25316791 Roulis M ; Nikolaou C ; Kotsaki E ; Kaffe E ; Karagianni N ; Koliaraki V ; Salpea K ; Ragoussis J ; Aidinis V ; Martini E ; Becker C ; Herschman HR ; Vetrano S ; Danese S ; Kollias G Proc Natl Acad Sci U S A 2014[Oct]; 111 (43 ): E4658-67 PMID25316791 show ga Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with inflammatory bowel diseases (IBDs). Here we show that Tpl2 may exert a dominant homeostatic rather than inflammatory function in the intestine mediated specifically by subepithelial intestinal myofibroblasts (IMFs). Mice with complete or IMF-specific Tpl2 ablation are highly susceptible to epithelial injury-induced colitis showing impaired compensatory proliferation in crypts and extensive ulcerations without significant changes in inflammatory responses. Following epithelial injury, IMFs sense innate or inflammatory signals and activate, via Tpl2, the cyclooxygenase-2 (Cox-2)-prostaglandin E2 (PGE2) pathway, which we show here to be essential for the epithelial homeostatic response. Exogenous PGE2 administration rescues mice with complete or IMF-specific Tpl2 ablation from defects in crypt function and susceptibility to colitis. We also show that Tpl2 expression is decreased in IMFs isolated from the inflamed ileum of IBD patients indicating that Tpl2 function in IMFs may be highly relevant to human disease. The IMF-mediated mechanism we propose also involves the IBD-associated genes IL1R1, MAPK1, and the PGE2 receptor-encoding PTGER4. Our results establish a previously unidentified myofibroblast-specific innate pathway that regulates intestinal homeostasis and may underlie IBD susceptibility in humans. |*Homeostasis/drug effects [MESH] |Animals [MESH] |Cell Lineage [MESH] |Cell Proliferation/drug effects [MESH] |Colitis/enzymology/immunology/pathology [MESH] |Cyclooxygenase 2/*metabolism [MESH] |Dextran Sulfate [MESH] |Dinoprostone/administration & dosage/*metabolism/pharmacology [MESH] |Disease Susceptibility [MESH] |Enzyme Activation/drug effects [MESH] |Epithelial Cells/drug effects/metabolism/pathology [MESH] |Epithelium/*metabolism/pathology [MESH] |Humans [MESH] |Immunity, Innate/drug effects [MESH] |Inflammation/pathology [MESH] |Inflammatory Bowel Diseases/enzymology/pathology [MESH] |Intestines/*pathology [MESH] |MAP Kinase Kinase Kinases/deficiency/*metabolism [MESH] |Mice, Inbred C57BL [MESH] |Models, Biological [MESH] |Myofibroblasts/drug effects/enzymology/*metabolism/pathology [MESH] |Phenotype [MESH] |Proto-Oncogene Proteins/deficiency/*metabolism [MESH]Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate(epmc).pdf DeepDyve Pubget Overpricing