Microglial activation by the small heat shock protein, alpha-crystallin.
Activated microglia regulate immune and inflammatory responses in the CNS under a variety of stresses due to infection, injury and disease. In this study, we show that a stress-inducible small heat shock protein, alpha-crystallin, induces in vitro activation of microglia cultured from newborn rat brain. Exposure of microglia to alpha-crystallin resulted in an increased production of nitric oxide (NO) and the expression of the inducible NO synthase (iNOS) as determined by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Alpha-crystallin also stimulated the synthesis of the pro-inflammatory cytokine, TNF alpha. The results presented showing microglial induction of the two key immune regulatory and inflammatory molecules, i.e., NO and TNF alpha, in response to a stress-inducible protein, suggest a link between environmental stress and the CNS immune response.
Bhat
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Department of Neurology, Medical University of South Carolina, Charleston 29425, USA.
Sharma
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D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000166:cytology; D002851:Chromatography, High Pressure Liquid; D003459:Crystallins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000037:antagonists & inhibitors; D020033:Protein Isoforms / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003459:Crystallins; D004791:Enzyme Inhibitors; D009573:Nitrites; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester