The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23-->IL-17 axis.
| Autoři: | Sheibanie AF; Department of Physiology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USA., Yen JH, Khayrullina T, Emig F, Zhang M, Tuma R, Ganea D |
|---|---|
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Jun 15; Vol. 178 (12), pp. 8138-47. |
| Způsob vydávání: | Journal Article; Research Support, N.I.H., Extramural |
| Jazyk: | English |
| Informace o časopise: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Print ISSN: 0022-1767 (Print) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| Výrazy ze slovníku MeSH: | Colitis/*immunology , Colon/*immunology , Dinoprostone/*metabolism , Inflammatory Bowel Diseases/*immunology , Interleukin-17/*metabolism , Interleukin-23/*metabolism, Animals ; Anti-Ulcer Agents/pharmacology ; Colitis/chemically induced ; Colon/drug effects ; Cytokines/metabolism ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dinoprostone/pharmacology ; Disease Models, Animal ; Inflammatory Bowel Diseases/chemically induced ; Interleukin-12/antagonists & inhibitors ; Interleukin-17/analysis ; Interleukin-23/analysis ; Interleukins/antagonists & inhibitors ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/immunology ; Lipopolysaccharides/immunology ; Lipopolysaccharides/pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Misoprostol/pharmacology ; Neutrophils/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; Trinitrobenzenesulfonic Acid/toxicity |
| Abstrakt: | 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. |
| Grant Information: | R01 AI 052306 United States AI NIAID NIH HHS |
| Substance Nomenclature: | 0 (Anti-Ulcer Agents) 0 (Cytokines) 0 (Il27 protein, mouse) 0 (Interleukin-17) 0 (Interleukin-23) 0 (Interleukins) 0 (Lipopolysaccharides) 0E43V0BB57 (Misoprostol) 187348-17-0 (Interleukin-12) 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) K7Q1JQR04M (Dinoprostone) |
| Entry Date(s): | Date Created: 20070606 Date Completed: 20070801 Latest Revision: 20220408 |
| Update Code: | 20240829 |
| DOI: | 10.4049/jimmunol.178.12.8138 |
| PMID: | 17548652 |
| Autor: | Sheibanie AF; Department of Physiology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USA., Yen JH, Khayrullina T, Emig F, Zhang M, Tuma R, Ganea D |
| Jazyk: | angličtina |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Jun 15; Vol. 178 (12), pp. 8138-47. |
| DOI: | 10.4049/jimmunol.178.12.8138 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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