Protective effect of resveratrol against LPS-induced extracellular lipoperoxidation in AR42J cells partly via a Myd88-dependent signaling pathway.
Lipopolysaccharides (LPS) are major components of the cell wall of Gram negative bacteria implicated in the pathogenesis of bacterial infection. Resveratrol is a polyphenolic phytoalexin exhibiting antioxidant and anti-inflammatory properties. We investigated the protective effects of this natural compound on LPS-induced proinflammatory effect using non-myeloid AR42J pancreatic cells. We found that LPS dose-dependently increased extracellular malondialdehyde (MDA) and nitric oxide without affecting their intracellular level whereas resveratrol abolished all these deleterious effects. LPS increased CD14 expression; IRAK1 and a phosphorylated form of p38 MAPK protein. Resveratrol counteracted LPS effect by decreasing CD14 and IRAK1 expression but unexpectedly increased the p38 MAPK protein phosphorylation. Altogether, our data highlighted the functionality of the TLR4-Myd88 signaling pathway in LPS pro-oxidant effect using non-myeloid cells. They further suggested that resveratrol exerted antioxidant properties either by a Myd88-dependent way not involving IRAK1 or by a TRIF dependent pathway.
Sebai
Hichem
H
INSERM UMR-911 CRO2, Aix-Marseille Université, Faculté de Médecine-Timone, 27 Bld Jean Moulin, 13385 Marseille Cedex 05, France. sebaihichem@yahoo.fr
Ristorcelli
Elodie
E
Sbarra
Veronique
V
Hovsepian
Sonia
S
Fayet
Guy
G
Aouani
Ezzedine
E
Lombardo
Dominique
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000187:drug effects; D051381:Rats; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D013267:Stilbenes; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D008315:Malondialdehyde; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077185:Resveratrol