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dc.contributor.authorPraveen Chansrichavalaen_US
dc.contributor.authorUdom Chantharaksrien_US
dc.contributor.authorPiyamitr Sritaraen_US
dc.contributor.authorNathamon Ngaosuwankulen_US
dc.contributor.authorSansanee C. Chaiyarojen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherChulabhorn Research Instituteen_US
dc.identifier.citationInternational Immunopharmacology. Vol.10, No.8 (2010), 892-899en_US
dc.description.abstractStatins, HMG-CoA reductase inhibitors, are used widely in the treatment of hypercholesterolemia. Apart from lowering lipid levels, statins have been shown to have anti-inflammatory effects. Previously we showed that atorvastatin inhibits NF-κB activation, dose and time dependently, in LPS-TLR4 signaling pathway. In this study, we investigated the anti-inflammatory mechanism of atorvastatin via Toll-like receptor 4 (TLR4) in murine pro-B cell lines transfected with TLR4. Co-treatment of LPS-stimulated cells with both atorvastatin and mevalonate rescued NF-κB activation and TLR4 blockade demonstrated that atorvastatin does not exert its inhibitory effect via TLR4 receptor-ligand binding mechanism. Further investigation into the anti-inflammatory mechanism has shown that atorvastatin causes an impairment of TLR4 recruitment into the lipid raft thereby affecting anti-inflammatory responses. In contrast, mevalonate repaired lipid raft function leading to TLR4 clustering in the lipid raft. Together, these data suggest that atorvastatin exerts its anti-inflammatory effect via lipid raft modification. This novel finding offers another insight into the pleiotropic effects of atorvastatin and may be applicable to other pattern recognition receptors that utilize membrane lipid raft as a platform for signal transduction. © 2010 Elsevier B.V.en_US
dc.rightsMahidol Universityen_US
dc.subjectImmunology and Microbiologyen_US
dc.subjectPharmacology, Toxicology and Pharmaceuticsen_US
dc.titleAtorvastatin affects TLR4 clustering via lipid raft modulationen_US
Appears in Collections:Scopus 2006-2010

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