title: CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis.
abstract: Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications.
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan. Electronic address: cwang@ocean.ag.
authors: Chao-Yung
authors: CY
authors: Wang
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Ming-Jer
authors: MJ
authors: Hsieh
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: I-Chang
authors: IC
authors: Hsieh
authors: Department of Infectious Diseases, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Shian-Sen
authors: SS
authors: Shie
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Ming-Yun
authors: MY
authors: Ho
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Jih-Kai
authors: JK
authors: Yeh
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Ming-Lung
authors: ML
authors: Tsai
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Chia-Hung
authors: CH
authors: Yang
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Kuo-Chun
authors: KC
authors: Hung
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
authors: Chun-Chieh
authors: CC
authors: Wang
authors: Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan. Electronic address: wenms123@gmail.com.
authors: Ming-Shien
authors: MS
authors: Wen
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000382:microbiology*; D000818:Animals; D056926:CLOCK Proteins / Q000172:deficiency / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007265:Inhibins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000382:microbiology*; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007265:Inhibins; D012313:RNA; D056926:CLOCK Proteins; C538944:Clock protein, mouse
keywords: Circadian rhythm; Inhibin; Lung injury; Polymicrobial infection; Sepsis