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

Overview

MeSH Major

  • Carbon Monoxide
  • Caveolin 1
  • Heme Oxygenase-1
  • Membrane Proteins
  • Signal Transduction
  • Toll-Like Receptor 4

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-alpha 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.

publication date

  • March 15, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.0712437

PubMed ID

  • 19265160

Additional Document Info

start page

  • 3809

end page

  • 18

volume

  • 182

number

  • 6