Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2

Morteau, Olivier; Morham, Scott G.; Sellon, Rance K.; Dieleman, Levinus A.; Langenbach, Robert; Smithies, Oliver; Sartor, R. Balfour

doi:10.1172/jci6899

Cited by 253 publications

(206 citation statements)

References 47 publications

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“…Cox-2−/− mice demonstrate increased susceptibility to DSS-induced colitis which correlates ith their inability to produce PGE 2 22 . Animals deficient in the PGE2 receptor, EP4, are more susceptible to DSS injury 55 .…”

Section: Discussionmentioning

confidence: 99%

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Cox-2 Is Regulated by Toll-Like Receptor-4 (TLR4) Signaling: Role in Proliferation and Apoptosis in the Intestine

Fukata¹,

Chen²,

Klepper³

et al. 2006

Gastroenterology

394

347

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Section: Discussionmentioning

confidence: 99%

“…Production of PGE 2 in the tissue culture supernatant was determined using a monoclonal EIA kit (Cayman, Ann Arbor, MI) according to the manufacturer's instructions and Morteau et al 22 . Briefly, colonic samples from TLR4−/− and WT mice were washed in cold PBS containing penicillin, streptomycin, and fungizone (100U/ml each).…”

Section: Measurement Of Pgementioning

confidence: 99%

Cox-2 Is Regulated by Toll-Like Receptor-4 (TLR4) Signaling: Role in Proliferation and Apoptosis in the Intestine

Fukata¹,

Chen²,

Klepper³

et al. 2006

Gastroenterology

394

347

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“…On the other hand, constitutive PGE 2 production in the intestine appears to have a protective effect on the integrity of the epithelial intestinal wall, presumably through the enhancement of epithelium survival and regeneration (45,64,65). This is evident primarily in models of colitis where the central event is damage to the epithelial layer, such as dextran sodium sulfate-induced colitis, and in experimental models using Cox1/2-or EP4-deficient mice, where PGE 2 synthesis or signaling of constitutive PGE 2 through the EP4 receptor are prevented (65)(66)(67). In agreement with previously reported deleterious effect of nonsteroidal anti-inflammatory drugs or Cox inhibitors in IBD, we found that use of the nonselective Cox inhibitor indomethacin had as drastic an effect in TNBS colitis as the administration of high doses of misoprostol or PGE 1 -OH.…”

Section: Discussionmentioning

confidence: 99%

The Proinflammatory Effect of Prostaglandin E2 in Experimental Inflammatory Bowel Disease Is Mediated through the IL-23→IL-17 Axis

Sheibanie

Yen

Khayrullina

et al. 2007

The Journal of Immunology

247

188

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Although Crohn’s disease has been traditionally considered to be Th1-mediated, the newly identified Th17 cells emerged recently as crucial participants. Th1/Th17 differentiation is controlled primarily by the IL-12 family of cytokines secreted by activated dendritic cells (DCs) and macrophages. IL-23 and IL-12/IL-27 have opposite effects, supporting the Th17 and Th1 phenotypes, respectively. We found that PGE2, a major lipid mediator released in inflammatory conditions, shifts the IL-12/IL-23 balance in DCs in favor of IL-23, and propose that high levels of PGE2 exacerbate the inflammatory process in inflammatory bowel disease through the IL-23→IL-17 axis. We assessed the effects of PGE2 on IL-12, IL-27, and IL-23 and found that PGE2 promotes IL-23, inhibits IL-12 and IL-27 expression and release from stimulated DCs, and subsequently induces IL-17 production in activated T cells. The effects of PGE2 are mediated through the EP2/EP4 receptors on DCs. In vivo, we assessed the effects of PGE analogs in an experimental model for inflammatory bowel disease and found that the exacerbation of clinical symptoms and histopathology correlated with an increase in IL-23 and IL-17, a decrease in IL-12p35 expression in colon and mesenteric lymph nodes, and a substantial increase in the number of infiltrating neutrophils and of CD4+IL-17+ T cells in the colonic tissue. These studies suggest that high levels of PGE2 exacerbate the inflammatory process through the preferential expression and release of DC-derived IL-23 and the subsequent support of the autoreactive/inflammatory Th17 phenotype.

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“…PGE 2 is a product of prostaglandin-endoperoxide synthase 2 (Ptgs2, also known as COX-2). Ptgs2-deficient mice show more colonic injury than WT controls upon DSS administration (13), and intraperitoneal injection of PGE 2 increases epithelial proliferation after DSS exposure in WT mice (14). The TLR/MyD88 signaling pathway positively regulates Ptgs2 (15,16), and in one study, isolated mesenchyme from DSS-treated descending colons revealed a MyD88-dependent induction of Ptgs2 mRNA (7).…”

Section: Innate Immune Recognition Of the Commensal Microflora As A Cmentioning

confidence: 96%

Prostaglandin-secreting cells: a portable first aid kit for tissue repair

Rakoff-Nahoum¹,

Medzhitov²

2007

J. Clin. Invest.

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Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2

Cited by 253 publications

References 47 publications

Cox-2 Is Regulated by Toll-Like Receptor-4 (TLR4) Signaling: Role in Proliferation and Apoptosis in the Intestine

Cox-2 Is Regulated by Toll-Like Receptor-4 (TLR4) Signaling: Role in Proliferation and Apoptosis in the Intestine

The Proinflammatory Effect of Prostaglandin E2 in Experimental Inflammatory Bowel Disease Is Mediated through the IL-23→IL-17 Axis

Prostaglandin-secreting cells: a portable first aid kit for tissue repair

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