title: Tetracycline inhibits local inflammation induced by cerebral ischemia via modulating autophagy.
abstract: BACKGROUND
  Tetracycline exerts neuroprotection via suppressing the local inflammation induced by cerebral ischemia. However, the underlying mechanism is not completely clear.
  
  
  RESULTS
  The 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
  Our 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.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Juehua
authors.initials: J
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Gelin
authors.initials: G
authors.lastname: Xu
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D000071186:Beclin-1; D002545:Brain Ischemia / Q000188:drug therapy*; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013752:Tetracycline / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000225:Adenine; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D015850:Interleukin-6; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013752:Tetracycline; D014409:Tumor Necrosis Factor-alpha; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C025946:3-methyladenine