Abstract
We utilized a model of myelin basic protein (MBP) activation in vivo and MBP-stimulated cultures in vitro to study the influence of TGF-beta1 on glial cell proliferation and ICAM-1/leucocyte function-associated antigen-1 (LFA-1) expression, and to observe the antagonistic effects of TGF-beta1 and IFN-gamma. TGF-beta1 inhibited MBP-stimulated and MBP-activated glial cell proliferation, especially in MBP-stimulated separated microglia and astrocytes, and down-regulated the expression of ICAM-1 on MBP-stimulated glial cells and separated microglia. ICAM-1 expression on MBP-activated glial cells was intensely suppressed, whereas its expression on MBP-stimulated astrocytes was not influenced. TGF-beta1 had no effect on LFA-1 expression. In contrast, IFN-gamma up-regulated ICAM-1 expression, but inhibited proliferative response on MBP-stimulated glial cells when cultured without TGF-beta1. Examination of TGF-beta1 and IFN-gamma interactions revealed that TGF-beta1-mediated inhibition of proliferation and down-regulation of ICAM-1 on glial cells were prevented by IFN-gamma. The suppressive effect was re-established with high doses of TGF-beta1 in cultures, indicating that biological effects of TGF-beta1 vary depending on nitric oxide (NO) production, its concentration in the microenvironment and regulation of the cytokine network.
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