Tristetraprolin Mediates Anti-Inflammatory Effect of Carbon Monoxide against DSS-Induced Colitis

Endogenous carbon monoxide (CO) exerts anti-inflammatory effects. Tristetraprolin (TTP) is known to destabilize proinflammatory transcripts. Here we found that exogenous CO enhanced the decay of TNF-alpha mRNA and suppressed TNF-alpha expression in LPS-activated macrophages from wild-type (WT) mice. However, TTP deficiency abrogated the effects of exogenous CO. While CO treatment prior to DSS administration in WT mice significantly reduced inflammatory cytokine levels and colitis, it failed to reduce the pro-inflammatory cytokine levels and colitis in TTP knockout (KO) mice. Our results demonstrate that TTP is a key factor mediating the anti-inflammatory action of CO in DSS-induced colitis.