Tristetraprolin mediates anti-inflammatory effects of carbon monoxide on lipopolysaccharide-induced acute lung injury.
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.
Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea.
Yeonsoo
Y
Joe
Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea.
Seul-Ki
SK
Kim
Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea.
Yingqing
Y
Chen
Department of Pathology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Jung Wook
JW
Yang
Department of Pathology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Jeong-Hee
JH
Lee
Department of Anatomy, School of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Gyeong Jae
GJ
Cho
Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea. Electronic address: jwpark@ulsan.ac.kr.
Jeong Woo
JW
Park
Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea. Electronic address: chung@ulsan.ac.kr.
Hun Taeg
HT
Chung
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051816:Tristetraprolin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051816:Tristetraprolin; D002248:Carbon Monoxide