Contribution of conjugated linoleic acid to the suppression of inducible nitric oxide synthase expression and transcription factor activation in stimulated mouse mesangial cells.
That both infiltrating macrophages and resident mesangial cells express inducible nitric oxide synthase (iNOS) and produce nitric oxide (NO) excessively is crucial to the progress of glomerulonephritis. Although several reports have mentioned the protective impacts of conjugated linoleic acid (CLA) in stimulated macrophages, the role of CLA in glomerular mesangial cells is unknown. The aim of the present study was to explore the ability of CLA to regulate iNOS expression and NO production in stimulated glomerular mesangial cells. Additionally, we evaluated the effect of CLA on activation of transcription factors which mediate iNOS expression. Exogenous CLA dose-dependently diminished iNOS mRNA and protein expression as well as NO production in lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated SV-40-transformed mouse mesangial cells. Electrophoretic mobility shift assay experiments demonstrated that CLA (100 microM) dramatically reduced activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) induced by LPS/IFN-gamma. Moreover, addition of 100 microM CLA significantly diminished LPS-IFN-gamma-induced protein degradation of inhibitor kappaB-alpha (IkappaB-alpha) and the protein expression of phosphorylated IkappaB-alpha in the cytosolic fraction as well as nuclear p65 expression (P < 0.05). In summary, inhibition of NF-kappaB, AP-1 and CREB activation by CLA may be associated with the molecular basis for which CLA suppresses iNOS expression and NO production in stimulated mesangial cells.
Sheu
Ji-Nan
JN
Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan, ROC.
Lin
Ting-Hui
TH
Lii
Chong-Kuei
CK
Chen
Chao-Chun
CC
Chen
Haw-Wen
HW
Liu
Kai-Li
KL
D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000633:toxicity; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II