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.
Two glial cell populations of the CNS, astrocytes and microglia, were examined for expression of two immunologically important molecules, MHC 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 elevated class II expression and NO in both cells. Genistein, an inhibitor of tyrosine kinases, and calphostin, an inhibitor of protein kinase C, diminished cytokine induction of class II MHC and NO in both glial populations. Forskolin was most effective in inhibiting class II MHC expression, but had little inhibitory effect on NO production. These results indicate microglia are more effective than astrocytes in producing cell-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.
Hellendall
R P
RP
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599-7295, USA. rph3681@email.unc.edu
Ting
J P
JP
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D016207:Cytokines; D004791:Enzyme Inhibitors; D000949:Histocompatibility Antigens Class II; D005576:Colforsin; D009569:Nitric Oxide; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C