Thymosin β4 inhibits microglia activation through microRNA 146a in neonatal rats following hypoxia injury.

Neuroinflammation mediated by activated microglia plays a pivotal role in the pathogenesis of neurological disorders, including hypoxic injury of the developing brain. Thymosin beta 4 (T beta 4), the major G-actin-sequestering molecule, has an anti-inflammatory effect and has been used to treat various neurological diseases. However, the effect of T beta 4 on hypoxia-induced microglia activation in the developing brain remains unclear. We investigate here the effect of T beta 4 on microglia activation of neonatal rats after hypoxia exposure. T beta 4 treatment was carried out on 1-day-old rats and BV-2 cells. T beta 4 expression in microglia was determined by quantitative real time-PCR, western blotting, and immunofluorescence staining. Secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and nitric oxide (NO) was assessed by enzyme-linked immunosorbent assay and colorimetric assay. mRNA expression of TNF-alpha and IL-1 beta, and microRNA 146a expression was determined by quantitative real time-PCR. We showed that T beta 4 treatment significantly inhibited secretion of inflammatory mediators in the cerebellum of neonatal rats following hypoxia injury. Increased expression of endogenous T beta 4 in microglia was observed both in hypoxic rats and in BV-2 cells. T beta 4 treatment significantly inhibited the expression and secretion of hypoxia-induced TNF-alpha, IL-1 beta, and NO. Remarkably, microRNA 146a expression was found to have increased in T beta 4-treated BV-2 cells. We demonstrated the anti-inflammatory effect of T beta 4 in neonatal rats following hypoxic brain injury. More importantly, our data reveal, for the first time, that T beta 4 inhibits microglia activation in vitro. Therefore, this study contributes to understanding the role and mechanism of T beta 4 function in central nervous system diseases. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.