G Protein-Coupled Receptor 43 Is Essential for Neutrophil Recruitment during Intestinal Inflammation.

Sina, C., Gavrilova, O., Forster, M., Till, A., Derer, S., Hildebrand, F., Raabe, B., Chalaris, A., Scheller, J., Rehmann, A., Franke, Andre, Ott, Stephan, Hasler, R., Nikolaus, S., Folsch, U. R., Rose-John, S., Jiang, H. P., Li, J., Schreiber, Stefan and Rosenstiel, Philip (2009) G Protein-Coupled Receptor 43 Is Essential for Neutrophil Recruitment during Intestinal Inflammation. Journal of Immunology, 183 (11). pp. 7514-7522.

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Abstract

Molecular danger signals attract neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) to sites of infection. The G protein-coupled receptor (GPR) 43 recognizes propionate and butyrate and is abundantly expressed on PMNs. The functional role of GPR43 activation for in vivo orchestration of immune response is unclear. We examined dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammatory response in wild-type and Gpr43-deficient mice. The severity of colonic inflammation was assessed by clinical signs, histological scoring, and cytokine production. Chemotaxis of wild-type and Gpr43-deficient PMNs was assessed through transwell cell chemotactic assay. A reduced invasion of PMNs and increased mortality due to septic complications were observed in acute DSS colitis. In chronic DSS colitis, Gpr43(-/-) animals showed diminished PMN intestinal migration, but protection against inflammatory tissue destruction. No significant difference in PMN migration and cytokine secretion was detected in a sterile inflammatory model. Ex vivo experiments show that GPR43-induced migration is dependent on activation of the protein kinase p38 alpha, and that this signal acts in cooperation with the chemotactic cytokine keratinocyte chemoattractant. Interestingly, shedding of L-selectin in response to propionate and butyrate was compromised in Gpr43(-/-) mice. These results indicate a critical role for GPR43-mediated recruitment of PMNs in containing intestinal bacterial translocation, yet also emphasize the bipotential role of PMNs in mediating tissue destruction in chronic intestinal inflammation. The Journal of Immunology, 2009, 183: 7514-7522.

Document Type: Article
Keywords: chain fatty-acidsactive crohns-disease genome-wide association cancer cell-line project rdp-ii bowel-disease anti-interleukin-12 antibody experimental colitis l-selectin tnf-alpha
Research affiliation: OceanRep > The Future Ocean - Cluster of Excellence
Kiel University
Refereed: Yes
ISSN: 0022-1767
Projects: Future Ocean
Date Deposited: 11 Feb 2011 12:15
Last Modified: 19 Apr 2013 12:26
URI: http://oceanrep.geomar.de/id/eprint/9739

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