The heme oxygenase-1/carbon monoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1

Xiao Mei Wang, Hong Pyo Kim, Kiichi Nakahira, Stefan W. Ryter, Augustine M.K. Choi

Research output: Contribution to journalArticle

170 Scopus citations

Abstract

Caveolin-1 (cav-1), the principle structural protein of plasmalemmal caveolae, regulates inflammatory signaling processes originating at the membrane. We show that cav-1 bound to TLR4 and inhibited LPS-induced proinflammatory cytokine (TNF-α and IL-6) production in murine macrophages. Mutation analysis revealed a cav-1 binding motif in TLR4, essential for this interaction and for attenuation of proinflammatory signaling. Cav-1 was required for the anti-inflammatory effects of carbon monoxide (CO), a product of heme oxygenase-1 (HO-1) activity. CO augmented the cav-1/TLR4 interaction. Upon LPS stimulation, HO-1 trafficked to the caveolae by a p38 MAPK-dependent mechanism, where it down-regulated proinflammatory signaling. These results reveal an anti-inflammatory network involving cav-1 and HO-1.

Original languageEnglish (US)
Pages (from-to)3809-3818
Number of pages10
JournalJournal of Immunology
Volume182
Issue number6
DOIs
StatePublished - Mar 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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