title: hCLOCK induction by hypoxia promotes inflammatory responses by activating the NF‑κB pathway.
abstract: The expression and secretion of infla-mmation‑associated cytokines are induced by hypoxia. Circadian locomotor output cycles protein kaput (CLOCK) has previously been shown to activate the nuclear factor‑κB (NF‑κB) pathway, which is a key transcription factor during hypoxia. The present study evaluated the role of the NF‑κB pathway in the CLOCK‑induced inflammatory response. Under hypoxic conditions, the expression levels of NF‑κB and proinflammatory cytokines, including interleukin (IL)‑1, IL‑1β, IL‑6, intercellular adhesion molecule 1, cyclooxygenase 2 and tumor necrosis factor alpha, were significantly increased compared with under control conditions. Conversely, human umbilical vein endothelial cells (HUVECs) that were transfected with small hairpin RNA against human CLOCK exhibited reversed effects. Furthermore, inhibition of NF‑κB with pyrrolidine dithiocarbamate (PDTC) reduced the expression of proinflammatory cytokines in HUVECs treated under hypoxic conditions. In addition, the CLOCK‑induced inflammatory response was abolished with PDTC treatment. These findings suggest that the mechanism by which CLOCK induces inflammation mainly involves activation of the NF‑κB signaling pathway.
authors.affiliation: Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Daqiao
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Changpo
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, P.R. China.
authors.forename: Ruizhe
authors.initials: R
authors.lastname: Qian
authors.affiliation: Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Vascular Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Vascular Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Longhua
authors.initials: L
authors.lastname: Fan
mesh_terms: D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D056926:CLOCK Proteins