IBD and prostaglandin E2

[Guest guest]

Dear All;

This recent paper adds to the growing evidence that the newly

discovered Th17 cells (T helper cells that produce interleukin 17)

play an important role in experimental inflammatory bowel disease. It

further shows that prostaglandin E2 plays an important role in

driving the production of this inflammatory Th17 cell type.

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J. Immunol. 2007 Jun 15;178(12):8138-47.

The Proinflammatory Effect of Prostaglandin E2 in Experimental

Inflammatory Bowel Disease Is Mediated through the IL-23->IL-17 Axis.

Sheibanie AF, Yen JH, Khayrullina T, Emig F, Zhang M, Tuma R, Ganea D

Department of Physiology, Temple University School of Medicine,

Philadelphia, PA 19140.

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

PGE(2), 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 PGE(2) exacerbate the inflammatory process in

inflammatory bowel disease through the IL-23-->IL-17 axis. We

assessed the effects of PGE(2) on IL-12, IL-27, and IL-23 and found

that PGE(2) 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 PGE(2) 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 PGE(2) 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. PMID: 17548652.

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Best regards,

Dave

(father of (22); PSC 07/03; UC 08/03)