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) |
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| Authors: | B.-G. XIAO G.-X. ZHANG C.-G. MA H. LINK |
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| Affiliation: | Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden |
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| 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-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. |
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| Keywords: | transforming growth factor-beta interferon-gamma intercellular adhesion molecule-1 LFA-1 glial cell culture |
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