Atorvastatin attenuates TLR4-mediated NF-kappaB activation in a MyD88-dependent pathway.
Antigen presenting cells such as dendritic cells and macrophages have recently been detected in atherosclerotic plaques. Toll-like receptors expressed on the surface of these cells, have been implicated in ongoing inflammatory responses in the plaques. In this study, we investigated the anti-inflammatory effect of atorvastatin, a lipid lowering drug, via Toll-like receptor 4 (TLR4) in vitro, employing murine pro-B cell lines transfected with hTLR4/MD2 and MyD88/hTLR4/MD2 systems. The results showed that atorvastatin at 10 microM significantly attenuated NF-kappaB activation within 24 hours while at lower doses of 0.1 and 1 microM, treatment time had to be prolonged up to 48 hours for a significant inhibition to occur. The inhibition of NF-kappaB was also observed in a cell line cotransfected with MyD88 and TLR4 suggesting that the attenuation of NF-kappaB by atorvastatin occurred in a MyD88 dependent fashion.
Chansrichavala
Praveen
P
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Chantharaksri
Udom
U
Sritara
Piyamitr
P
Chaiyaroj
Sansanee C
SC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000069059:Atorvastatin; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D000893:Anti-Inflammatory Agents; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; C495377:LY96 protein, human; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011758:Pyrroles; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000069059:Atorvastatin