Tetracycline Inhibits Local Inflammation Induced by Cerebral Ischemia via Modulating Autophagy |
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| Authors: | Yongjun Jiang Juehua Zhu Li Wu Gelin Xu Jianwu Dai Xinfeng Liu |
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| Affiliation: | 1. Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province, China.; 2. Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, PR China.; University of North Dakota, United States of America, |
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| Abstract: | BackgroundTetracycline exerts neuroprotection via suppressing the local inflammation induced by cerebral ischemia. However, the underlying mechanism is not completely clear.Methodology/Principal FindingsThe mRNA and protein expressions of tumor necrosis factor α and interleukin 6 and the number of activated microglia were measured to detect the inflammatory process in the ischemic hemisphere. The key proteins of nuclear factor kappa B pathway and the binding activity of nuclear factor kappa B were also measured. Two key components of autophagy, Beclin 1 and LC3, were detected by western blotting. Pretreatment with tetracycline inhibited the mRNA and protein expressions of tumor necrosis factor α and interleukin 6 and decreased the numbers of activated and phagocytotic microglia. Tetracycline down regulated the total and phosphorylated expressions of IKK, IκB and p65 (P<0.05). The autophagy inhibitor, 3-methyladenine, inhibited inflammation and activation of nuclear factor kappa B pathway. The levels of Beclin 1 and LC3 were decreased by 3-methyladenine and tetracycline.Conclusions/SignificanceOur data suggested that pretreatment of tetracycline may inhibit autophagy in the ischemic stroke brain and then suppress the inflammatory process via inhibiting the activation of nuclear factor kappa B pathway. |
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