Effects of dexamethasone on microglial activation in vivo: selective downregulation of major histocompatibility complex class II expression in regenerating facial nucleus.
Following axotomy of the facial nerve microglial cells in the facial nucleus become activated, proliferate, and newly express class I and class II major histocompatibility complex (MHC) antigens. Dexamethasone treatment, starting 2 days prior to axotomy at 1 mg/kg/day, selectively inhibited axotomy-induced MHC class II expression on microglial and perivascular cells. In contrast, MHC class I expression was not significantly affected, nor was the expression of other microglial activation markers and the light microscopic morphology of activated microglia. A recently suggested inducer of MHC expression in rat nervous tissue, neuronal gamma interferon-like immunoreactive material, was also unaffected, as was glial fibrillary acidic protein immunoreactivity as a marker for concomitant astroglial activation. The differential effects of the drug suggest the presence of distinct regulatory pathways for different aspects of microglial activation. Inhibition of class II expression on activated microglia might be one mechanism how glucocorticoids act in the suppression of neuroinflammatory disease.
Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, F.R.G.
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Kiefer
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Kreutzberg
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D008297:Male; D009416:Nerve Regeneration; D009457:Neuroglia / Q000187:drug effects* / Q000276:immunology; D011149:Pons / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D000949:Histocompatibility Antigens Class II; D003907:Dexamethasone; D007371:Interferon-gamma