Document Detail

Differential modulation of Nods signaling pathways by fatty acids in human colonic epithelial HCT116 cells.
MedLine Citation:
PMID:  17303577     Owner:  NLM     Status:  MEDLINE    
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-kappaB 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-kappaB 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-kappaB 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-kappaB 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.
Ling Zhao; Myung-Ja Kwon; Shurong Huang; Joo Y Lee; Koichi Fukase; Naohiro Inohara; Daniel H Hwang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-02-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  282     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-16     Completed Date:  2007-05-31     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11618-28     Citation Subset:  IM    
Western Human Nutrition Research Center, The Agricultural Research Service-United States Department of Agriculture, Davis, California 95616, USA.
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MeSH Terms
Cell Line
Colon / cytology*
Epithelial Cells / cytology*
Fatty Acids / metabolism*
Gene Expression Regulation*
Inflammation / pathology
Interleukin-8 / biosynthesis,  metabolism
Lauric Acids / metabolism
NF-kappa B / metabolism
Nod1 Signaling Adaptor Protein / metabolism
Nod2 Signaling Adaptor Protein / metabolism
Protein Structure, Tertiary
Signal Transduction*
Transcriptional Activation
Grant Support
Reg. No./Substance:
0/Fatty Acids; 0/Interleukin-8; 0/Lauric Acids; 0/NF-kappa B; 0/NOD1 protein, human; 0/NOD2 protein, human; 0/Nod1 Signaling Adaptor Protein; 0/Nod2 Signaling Adaptor Protein; 143-07-7/lauric acid

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