Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway.
Data from a number of researchers have shown that conjugated linoleic acid (CLA) has some beneficial health activities in animal models. Because inflammatory responses are associated with pathophysiology of many diseases, the aim of this study is to explore the effect and mechanism of CLA in the regulation of lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. The addition of increasing levels of CLA proportionally augmented the incorporation of CLA in cultures. CLA diminished LPS-induced mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) as well as subsequent production of nitric oxide and prostaglandin E(2), respectively. We further examined the effect of CLA on LPS-induced NF-kappaB activation by Western blot and the electrophoretic mobility shift assay. The addition of CLA at 200 microM significantly diminished LPS-induced protein expression of the cytoplasmic phosphorylated inhibitor kappaBalpha and nuclear p65 as well as NF-kappaB nuclear protein-DNA binding affinity. In conclusion, our data suggest that CLA may inhibit LPS-induced inflammatory events in RAW 264.7 macrophages and this inhibitory activity of CLA, at least in part, occurs through CLA modulating the NF-kappaB activation and therefore negatively regulating expression of inflammatory mediators.
Cheng
Wen-Ling
WL
Departments of Nutrition and Life Sciences, Chung Shan Medical University, Number 110, Section 1, Chien-Kuo North Road, Taichung 40203, Taiwan, Republic of China.
Lii
Chong-Kuei
CK
Chen
Haw-Wen
HW
Lin
Ting-Hui
TH
Liu
Kai-Li
KL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2; D004247:DNA / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005227:Fatty Acids / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D007527:Isoenzymes; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D012333:RNA, Messenger; D004247:DNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone