Transforming growth factor-beta 1 (TGF-β1)-mediated inhibition of glial cell proliferation and down-regulation of intercellular adhesion molecule-1 (ICAM-1) are interrupted by interferon-gamma (IFN-γ)

Abstract

SUMMARY We utilized a model of myelin basic protein (MBP) activation in vivo and MBP-stimulated cultures in vitro to study the influence of TGF-β1 on glial cell proliferation and ICAM-1/leucocyte function-associated antigen-1 (LFA-1) expression, and to observe the antagonistic effects of TGF-β1 and IFN-γ. TGF-β1 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-β1 had no effect on LFA-1 expression. In contrast, IFN-γ up-regulated ICAM-1 expression, but inhibited proliferative response on MBP-stimulated glial cells when cultured without TGF-β1. Examination of TGF-β1 and IFN-γ interactions revealed that TGF-β1-mediated inhibition of proliferation and down-regulation of ICAM-1 on glial cells were prevented by IFN-γ. The suppressive effect was re-established with high doses of TGF-β1 in cultures, indicating that biological effects of TGF-β1 vary depending on nitric oxide (NO) production, its concentration in the microenvironment and regulation of the cytokine network.