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

J. Biol. Chem., Vol. 282, Issue 16, 11618-11628, April 20, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/16/11618    most recent M608644200v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhao, L. Articles by Hwang, D. H. Search for Related Content PubMed PubMed Citation Articles by Zhao, L. Articles by Hwang, D. H. Social Bookmarking                      What's this?

Differential Modulation of Nods Signaling Pathways by Fatty Acids in Human Colonic Epithelial HCT116 Cells^*

Ling Zhao, Myung-Ja Kwon, Shurong Huang, Joo Y. Lee, Koichi Fukase^¶, Naohiro Inohara^||, and Daniel H. Hwang¹

From the Western Human Nutrition Research Center, The Agricultural Research Service-United States Department of Agriculture, and Department of Nutrition, University of California, Davis, California 95616, the Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea, the ^¶Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan, and the ^||Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109

Nucleotide-binding oligomerization domain-containing proteins (Nods) are intracellular pattern recognition receptors recognizing conserved moieties of bacterial peptidoglycan through their leucine-rich repeats domain. The agonists for Nods activate proinflammatory signaling pathways, including NF-B pathways. The results from our previous studies showed that the activation of TLR4 and TLR2, leucine-rich repeat-containing pattern recognition receptors, were differentially modulated by saturated and n-3 polyunsaturated fatty acids in macrophages and dendritic cells. Here, we show the differential modulation of NF-B activation and interleukin-8 (IL-8) expression in colonic epithelial cells HCT116 by saturated and unsaturated fatty acids mediated through Nods proteins. Lauric acid (C12:0) dose dependently activated NF-B and induced IL-8 expression in HCT116 cells, which express both Nod1 and Nod2, but not detectable amounts of TLR2 and TLR4. These effects of lauric acid were inhibited by dominant negative forms of Nod1 or Nod2, but not by dominant negative forms of TLR2, TLR4, and TLR5. The effects of lauric acid were also attenuated by small RNA interference targeting Nod1 or Nod2. In contrast, polyunsaturated fatty acids, especially n-3 polyunsaturated fatty acids, inhibited the activation of NF-B and IL-8 expression induced by lauric acid or known Nods ligands in HCT116. Furthermore, lauric acid induced, but docosahexaenoic acid inhibited lauric acid- or Nod2 ligand MDP-induced, Nod2 oligomerization in HEK293T cells transfected with Nod2. Together, these results provide new insights into the role of dietary fatty acids in modulating inflammation in colon epithelial cells. The results suggest that Nods may be involved in inducing sterile inflammation, one of the key etiological conditions in the development of many chronic inflammatory diseases.

Received for publication, September 7, 2006 , and in revised form, February 12, 2007.

^* This work was supported by Grants DK064007, DK41868, and CA75613 from the National Institutes of Health, Grant 2001-35200-10721 from the United States Department of Agriculture (USDA), Grant 01A095Rev from the American Institutes for Cancer Research, and program funds from the Western Human Nutrition Research Center/Agricultural Research Service (ARS)/USDA. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: USDA/ARS, Western Human Nutrition Research Center and Dept. of Nutrition, University of California-Davis, 430 West Health Science Drive, One Shields Ave., Davis, CA 95616. Tel.: 530-754-4838; Fax: 530-752-5295; E-mail: dhwang{at}whnrc.usda.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Huang, L. Zhao, K. Kim, D. S. Lee, and D. H. Hwang Inhibition of Nod2 Signaling and Target Gene Expression by Curcumin Mol. Pharmacol., July 1, 2008; 74(1): 274 - 281. [Abstract] [Full Text] [PDF]