hCLOCK induction by hypoxia promotes inflammatory responses by activating the NF‑κB pathway

Tang,Xiao; Guo,Daqiao; Lin,Changpo; Shi,Zhenyu; Qian,Ruizhe; Fu,Weiguo; Liu,Jianjun; Li,Xu; Fan,Longhua

doi:10.3892/mmr.2017.6127

hCLOCK induction by hypoxia promotes inflammatory responses by activating the NF‑κB pathway

Authors:
- Xiao Tang
- Daqiao Guo
- Changpo Lin
- Zhenyu Shi
- Ruizhe Qian
- Weiguo Fu
- Jianjun Liu
- Xu Li
- Longhua Fan
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Affiliations: Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, P.R. China, Department of Vascular Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: January 17, 2017 https://doi.org/10.3892/mmr.2017.6127
Pages: 1401-1406

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Abstract

The expression and secretion of inflammation‑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.

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