Inflammatory signals induce the expression of tonicity-responsive enhancer binding protein (TonEBP) in microglia

J Neuroimmunol. 2016 Jun 15:295-296:21-9. doi: 10.1016/j.jneuroim.2016.04.009. Epub 2016 Apr 13.

Abstract

Tonicity-responsive enhancer (TonE) binding protein (TonEBP) is known as an osmosensitive transcription factor that regulates cellular homeostasis during states of hypo- and hypertonic stress. In addition to its role in osmoadaptation, growing lines of evidence suggest that TonEBP might have tonicity-independent functions. In particular, a number of studies suggest that inflammatory stimuli induce the expression and activation of TonEBP in peripheral immune cells. However, whether TonEBP is expressed in microglia, resident immune cells of the central nervous system, is unknown. Here we show that inflammatory signals induce the expression of TonEBP in microglia both in vitro and in vitro. In cultured primary microglia, treatment with lipopolysaccharide (LPS), interferon-γ, and interleukin 4 increased the expression of TonEBP. Moreover, we found that stereotaxic injection of LPS into the substantia nigra region of rat brain increased TonEBP expression in OX-42-positive cells. Furthermore, expression of TonEBP was induced in OX-42-positive cells in a rat model of transient middle cerebral artery occlusion. Together these results show that the expression of TonEBP is regulated by inflammatory signals in mammalian brain, suggesting that TonEBP might play a part during neuroinflammation.

Keywords: LPS; Microglia; Neuroinflammation; TonEBP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen / metabolism
  • Disease Models, Animal
  • Encephalitis / chemically induced
  • Encephalitis / pathology*
  • Female
  • Gene Expression Regulation / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Interferon-gamma / pharmacology
  • Interleukin-4 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mesencephalon / pathology*
  • Microglia / drug effects
  • Microglia / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • CD11b Antigen
  • Glial Fibrillary Acidic Protein
  • Lipopolysaccharides
  • Nfat5 protein, rat
  • RNA, Messenger
  • Transcription Factors
  • Interleukin-4
  • Interferon-gamma