Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6.
The central nervous system contains two major glial cell types, astrocytes and microglia, which function as immune effector cells within the central nervous system. We have been studying the ability of glial cells to express gene products involved in immune responsiveness, with an emphasis on expression of ICAM-1. We demonstrated previously that three proinflammatory cytokines, TNF-alpha, IL-1 beta, and IFN-gamma, as well as IFN-gamma plus LPS, can enhance ICAM-1 expression by primary rat astrocytes. In this study, we examined ICAM-1 expression by primary rat microglia and found that only IFN-gamma and IFN-gamma/LPS enhance ICAM-1 gene expression. These data indicate that ICAM-1 expression by astrocytes and microglia is enhanced differentially by various proinflammatory cytokines. We next examined the effect of two cytokines, IL-10 and IL-6, on ICAM-1 expression. IL-10 alone has no effect on ICAM-1 expression, but it inhibits the enhancement of ICAM-1 intracellular and membrane protein expression in both cell types, although it has no influence on ICAM-1 steady-state mRNA levels. These results suggest that IL-10 affects ICAM-1 expression at the translational and/or post-translational level. IL-6 alone also had no effect on ICAM-1 expression in either astrocytes or microglia, but it inhibited induction of both ICAM-1 mRNA and protein expression in these cells. Inhibition of ICAM-1 mRNA steady-state levels by IL-6 was not the result of degradation of the ICAM-1 message, suggesting an effect at the transcriptional level. Thus, both IL-10 and IL-6 can inhibit ICAM-1 expression by glial cells, although they do so by contrasting mechanisms.
Shrikant
P
P
Department of Cell Biology, University of Alabama at Birmingham 35294, USA.
Weber
E
E
Jilling
T
T
Benveniste
E N
EN
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003864:Depression, Chemical; D005786:Gene Expression Regulation / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007371:Interferon-gamma