The Heme Oxygenase-1/Carbon Monoxide Pathway Suppresses TLR4 Signaling by Regulating the Interaction of TLR4 with Caveolin-1 | Zendy

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

Open Access

The Heme Oxygenase-1/Carbon Monoxide Pathway Suppresses TLR4 Signaling by Regulating the Interaction of TLR4 with Caveolin-1

Author(s) -

Xiao Mei Wang,

Hong Pyo Kim,

Kiichi Nakahira,

Stefan W. Ryter,

Augustine M.K. Choi

Publication year - 2009

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.0712437

Subject(s) - proinflammatory cytokine , heme oxygenase , tlr4 , microbiology and biotechnology , caveolae , heme , chemistry , signal transduction , inflammation , biology , biochemistry , immunology , enzyme

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.

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