HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Ning, W. Articles by Li, C. Search for Related Content PubMed PubMed Citation Articles by Ning, W. Articles by Li, C.

Carbon monoxide inhibits IL-17-induced IL-6 production through the MAPK pathway in human pulmonary epithelial cells

¹Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and ²Jiangsu Key Laboratory for Molecular Medical Biotechnology, Life Sciences College, Nanjing Normal University, Nanjing, China

Submitted 11 May 2004 ; accepted in final form 21 March 2005

Interleukin (IL)-17 is a proinflammatory cytokine that is produced by activated memory CD4 T cells, which regulates pulmonary neutrophil emigration by the induction of CXC chemokines and cytokines. IL-17 constitutes a potential target for pharmacotherapy against exaggerated neutrophil recruitment in airway diseases. As a cytoprotective and anti-inflammatory gaseous molecule, carbon monoxide (CO) may also regulate IL-17-induced inflammatory responses in pulmonary cells. Herein, we examine the production of cytokine IL-6 induced by IL-17 and the effect of CO on IL-17-induced IL-6 production in human pulmonary epithelial cell A549. We first show that IL-17 can induce A549 cells to release IL-6 and that CO can markedly inhibit IL-17-induced IL-6 production. IL-17 activated the ERK1/2 MAPK pathway but did not affect p38 and JNK MAPK pathways. CO exposure selectively attenuated IL-17-induced ERK1/ERK2 MAPK activation without significantly affecting either JNK or p38 MAPK activation. Furthermore, in the presence of U0126 and PD-98059, selective inhibitors of MEK1/2, IL-17-induced IL-6 production was significantly attenuated. We conclude that CO inhibits IL-17-stimulated inflammatory response via the ERK1/2-dependent pathway.

interleukin-17; interleukin-6; inflammation; mitogen-activated protein kinase

This article has been cited by other articles:

				E. Masini, A. Vannacci, P. Failli, R. Mastroianni, L. Giannini, M. C. Vinci, C. Uliva, R. Motterlini, and P. F. Mannaioni A carbon monoxide-releasing molecule (CORM-3) abrogates polymorphonuclear granulocyte-induced activation of endothelial cells and mast cells FASEB J, September 1, 2008; 22(9): 3380 - 3388. [Abstract] [Full Text] [PDF]

				S. Dragon, M. S. Rahman, J. Yang, H. Unruh, A. J. Halayko, and A. S. Gounni IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L1023 - L1029. [Abstract] [Full Text] [PDF]