Tristetraprolin mediates anti-inflammatory effects of carbon monoxide on lipopolysaccharide-induced acute lung injury

The American Journal of Pathology
Yeonsoo JoeHun Taeg Chung

Abstract

Low-dose inhaled carbon monoxide is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the precise mechanism by which carbon monoxide confers protection against ALI is not clear. Tristetraprolin (TTP; official name ZFP36) exerts anti-inflammatory effects by enhancing decay of proinflammatory cytokine mRNAs. With the use of TTP knockout mice, we demonstrate here that the protection by carbon monoxide against LPS-induced ALI is mediated by TTP. Inhalation of carbon monoxide substantially increased the pulmonary expression of TTP. carbon monoxide markedly enhanced the decay of mRNA-encoding inflammatory cytokines, blocked the expression of inflammatory cytokines, and decreased tissue damage in LPS-treated lung tissue. Moreover, knockout of TTP abrogated the anti-inflammatory and tissue-protective effects of carbon monoxide in LPS-induced ALI. These results suggest that carbon monoxide-induced TTP mediates the protective effect of carbon monoxide against LPS-induced ALI by enhancing the decay of mRNA encoding proinflammatory cytokines.

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Citations

Feb 8, 2019·Brain and Behavior·Peiyu LiHongwei Gao
Jan 4, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yeonsoo JoeHun Taeg Chung
Oct 27, 2017·Wiley Interdisciplinary Reviews. RNA·Wendy Ezegbunam, Robert Foronjy
Nov 15, 2018·Oxidative Medicine and Cellular Longevity·Jeongmin ParkHun Taeg Chung
Sep 22, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiang SunShizhong Zhang
Jun 1, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Xichun WangYu Li

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