title: Function of Thymosin Beta-4 in Ethanol-Induced Microglial Activation.
abstract: OBJECTIVE
  Neuroinflammation mediated by activated microglia may play a pivotal role in a variety of central nervous system (CNS) pathologic conditions, including ethanol-induced neurotoxicity. The purpose of this study was to investigate the function of Tβ4 in ethanol-induced microglia activation.
  
  
  METHODS
  Quantitative real-time PCR was conducted to assess the expression of Tβ4 and miR-339-5p. Western blot analysis was used to measure the expression of Tβ4, phosphorylated p38, ERK, JNK, Akt, and NF-x03BA;B p65. The concentration of TNF-α and IL-1β was determined using ELISA. NO concentration was measured using a nitric oxide colorimetric BioAssay Kit. Double immunofluorescence was performed to determine Tβ4 expression, in order to assess microglial activation in neonatal mouse FASD model.
  
  
  RESULTS
  Increased Tβ4 expression was observed in ethanol treated microglia. Knockdown of Tβ4 enhanced ethanol-induced inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and nitric oxide (NO) in BV-2 cells was performed. Exogenous Tβ4 treatment significantly inhibited expression and secretion of these inflammatory mediators. Tβ4 treatment attenuated p38, ERK MAPKs, and nuclear factor-kappa B (NF-x03BA;B) pathway activation, and enhanced miR-339-5p expression induced by ethanol exposure in microglia. A neonatal mouse fetal alcohol spectrum disorders (FASD) model showed that Tβ4 expression in the microglia of the hippocampus was markedly enhanced, while Tβ4 treatment effectively blocked the ethanol-induced increase in inflammatory mediators, to the level expressed in vehicle-treated control animals.
  
  
  CONCLUSIONS
  This study is the first to demonstrate the function of Tβ4 in ethanol-induced microglia activation, thus contributing to a more robust understanding of the role of Tβ4 treatment in CNS disease.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wu
authors.forename: Weichen
authors.initials: W
authors.lastname: Zeng
authors.forename: Kai
authors.initials: K
authors.lastname: Yao
authors.forename: Hengbing
authors.initials: H
authors.lastname: Zu
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013947:Thymosin / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation; D000099201:Thymosin beta(4)
chemical_list: D000431:Ethanol; D053583:Interleukin-1beta; D016328:NF-kappa B; D009569:Nitric Oxide; D034741:RNA, Small Interfering; D013947:Thymosin; D014409:Tumor Necrosis Factor-alpha; D000099201:Thymosin beta(4)