Capsaicin attenuates LPS-induced inflammatory cytokine production by upregulation of LXRα

• Capsaicin inhibits LPS-induced pro-inflammatory cytokine production.
• Capsaicin upregulates LXRα expression through PPARγ pathway.
• LXRα participates in the inhibitory effects of capsaicin on LPS-induced pro-inflammatory cytokine production.
• LXRα participates in the inhibitory effects of capsaicin on NF-κB activation.

Here, we investigated the role of LXRα in capsaicin mediated anti-inflammatory effects. Results revealed that capsaicin inhibits LPS-induced IL-1β, IL-6 and TNF-α production in a time- and dose-dependent manner. Moreover, capsaicin increases LXRα expression through PPARγ pathway. Inhibition of LXRα activation by siRNA diminished the inhibitory action of capsaicin on LPS-induced IL-1β, IL-6 and TNF-α production. Additionally, LXRα siRNA abrogated the inhibitory action of capsaicin on p65 NF-κB protein expression. Thus, we propose that the anti-inflammatory effects of capsaicin are LXRα dependent, and LXRα may potentially link the capsaicin mediated PPARγ activation and NF-κB inhibition in LPS-induced inflammatory response.