Study on the mechanism of JAK2/STAT3 signaling pathway-mediated inflammatory reaction after cerebral ischemia

Wu,Yuquan; Xu,Juan; Xu,Jing; Zheng,Wei; Chen,Qingyong; Jiao,Deming

doi:10.3892/mmr.2018.8477

Study on the mechanism of JAK2/STAT3 signaling pathway-mediated inflammatory reaction after cerebral ischemia

Authors:
- Yuquan Wu
- Juan Xu
- Jing Xu
- Wei Zheng
- Qingyong Chen
- Deming Jiao
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Affiliations: Department of Geriatrics, The 117th Hospital of PLA, Hangzhou, Zhejiang 310013, P.R. China, Department of Clinical Laboratory, Hangzhou Clinical College of The People's Liberation Army of Anhui Medical University, Hangzhou, Zhejiang 310013, P.R. China
Published online on: January 24, 2018 https://doi.org/10.3892/mmr.2018.8477
Pages: 5007-5012
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the mechanism by which the Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway mediates cerebral ischemia and the efficacy of pharmaceutical intervention. The rat model of middle cerebral artery occlusion (MCAO) was established and confirmed via assessment of changes in the expression of phosphorylated (p)‑JAK2, p‑STAT3, high‑mobility group box 1 (HMGB1), and inflammatory factors using ELISA and western blot analysis. The effects of JAK2/STAT3 inhibitor and curcumin on the expression of p‑JAK2, p‑STAT3, HMGB1, and inflammatory factors after cerebral ischemia were observed with ELISA, western blotting and immunohistochemical staining. The concentrations of tumor necrosis factor (TNF)‑α and HMGB1 in brain tissue homogenate of MCAO group were significantly higher than in the sham group (P<0.01). The concentration of p‑JAK2/JAK2 and p‑STAT3/STAT3 in the brain tissue homogenate of MCAO group was significantly higher than in the sham group (P<0.05). The concentrations of TNF‑α, interleukin (IL)‑1β, IL‑6, and HMGB1 in the group treated with STAT3 inhibitor (MCAO + rapamycin), JAK2 inhibitor (MCAO + AG490), and MCAO + curcumin were significantly lower than in the MCAO group (P<0.01), as well as the relative content of p‑JAK2/JAK2 and p‑STAT3/STAT3 (P<0.05). Inhibition of the JAK2/STAT3 signaling pathway, such as curcumin can reduce the expression of HMGB1 in brain tissue after cerebral ischemia, which can significantly reduce the inflammatory response after cerebral ischemia.

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