DIFFERENTIAL REGULATION OF CYTOKINE-INDUCED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EXPRESSION AND NITRIC-OXIDE RELEASE IN RAT MICROGLIA AND ASTROCYTES BY EFFECTORS OF TYROSINE KINASE, PROTEIN-KINASE-C, AND CAMP
Rp. Hellendall et Jpy. Ting, DIFFERENTIAL REGULATION OF CYTOKINE-INDUCED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EXPRESSION AND NITRIC-OXIDE RELEASE IN RAT MICROGLIA AND ASTROCYTES BY EFFECTORS OF TYROSINE KINASE, PROTEIN-KINASE-C, AND CAMP, Journal of neuroimmunology, 74(1-2), 1997, pp. 19-29
Two glial cell populations of the CNS, astrocytes and microglia, were
examined for expression of two immunologically important molecules, MH
C class II and nitric oxide (NO), following treatment with cytokines.
IFN-gamma induced both molecules in microglia at substantially higher
levels than astrocytes. The addition of TNF-alpha to IFN-gamma elevate
d class LT expression and NO in both cells. Genistein, an inhibitor of
tyrosine kinases, and calphostin, an inhibitor of protein kinase C, d
iminished cytokine induction of class II MHC and NO in both glial popu
lations. Forskolin was most effective in inhibiting class II MHC expre
ssion, but had little inhibitory effect on NO production. These result
s indicate microglia are more effective than astrocytes in producing c
ell-associated and secreted immune mediators in response to IFN-gamma
and or TNF-alpha and multiple parallel, but distinct, signaling events
are required for cytokine induced class II MHC or NO production.