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

Yeonsoo Joe,Hyo Jeong Kim,Yingqing Chen,Hun Taeg Chung,Jeong Woo Park,Gyeong Jae Cho,Md Jamal Uddin,Nal Ae Yoon,Min Zheng,Benoit Foligne

doi:10.1371/journal.pone.0088776

Yeonsoo Joe, Hyo Jeong Kim + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0088776

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Abstract

Endogenous carbon monoxide (CO) exerts anti-inflammatory effects. Tristetraprolin (TTP) is known to destabilize pro-inflammatory transcripts. Here we found that exogenous CO enhanced the decay of TNF-α mRNA and suppressed TNF-α 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.

Highlights

Endogenous carbon monoxide (CO) is one of the three products of heme degradation created by heme oxygenase-1 (HO-1), the other two being Fe2+ and biliverdin [1]
TTP enhances degradation of various inflammatory cytokines [18,19,20]. This prompted us to evaluate the functional link between CO and TTP in macrophages, with the hypothesis that CO increases the expression of TTP, which in turn mediates the anti-inflammatory activity of CO by enhancing the degradation of mRNAs of inflammatory cytokine genes
The administration of CO or CO-RMs can inhibit the production of inflammatory cytokines and protect animals against inflammatory diseases [3]

Summary

Introduction

Endogenous CO is one of the three products of heme degradation created by heme oxygenase-1 (HO-1), the other two being Fe2+ and biliverdin [1]. These byproducts have recently been shown to have strong cytoprotective effects. This is thought to result from their anti-inflammatory, anti-apoptotic, and antioxidant actions [2]. Recent studies have shown that the exogenous application of CO or CO-releasing molecules (CORMs) can confer protective effects in models of inflammatory stress or tissue injury [3]. CO might be a novel and important molecule in the treatment of intestinal inflammation

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