Reciprocal Modulation of Nods Signalling Pathways by Saturated and n‐3 Polyunsaturated fatty acids in Human Colonic Epithelial HCT116 Cells

• Published in: The FASEB journal 2007, Vol.21 (6), p.LB41-LB41
• Main Authors: Zhao, Ling, Kwon, Myung Ja, Huang, Shurong, Lee, Joo Y., Fukase, Koichi, Inohara, Naohiro, Hwang, Daniel
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.LB41

Nucleotide‐binding oligomerization domain containing proteins (Nods) are intracellular pattern recognition receptors (PRRs) that recognize conserved moieties of bacterial peptidoglycan and induce inflammatory responses. We have shown that the activation of TLR4 and TLR2 were differentially modulated by saturated and n‐3 polyunsaturated fatty acids in macrophages and dendritic cells. Here, we show the reciprocal modulation of Nods signaling pathways by saturated and n‐3 polyunsaturated fatty acids in colonic epithelial cells HCT116, which express both Nod1 and Nod2, but not detectable amount of TLR2 and TLR4. Saturated fatty acids(C10:0, C12:0, C14:0) activated NF‐κB and induced IL‐8 expression while n‐3 PUFA inhibited the activation of NF‐κB and IL‐8 expression induced by lauric acid or known Nods ligand, i.e., iE‐DAP and MDP for Nod1 and Nod2, respectively. These effects are mediated through Nod1 and Nod2. Our results provide new insights into the role of dietary fatty acids in modulating inflammation in colon epithelial cells and suggest that Nods may be involved in inducing sterile inflammation, one of the key etiological conditions in the development of many chronic inflammatory diseases. This work was supported by NIH grants, grant (2001‐35200‐10721) from USDA, grant (01A095Rev) from the American Institutes for Cancer Research, and program funds from the WHNRC/ARS/USDA.