Transforming growth factor-beta 1 (TGF-beta1)-mediated inhibition of glial cell proliferation and down-regulation of intercellular adhesion molecule-1 (ICAM-1) are interrupted by interferon-gamma (IFN-gamma).
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.
Xiao
B G
BG
Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Zhang
G X
GX
Ma
C G
CG
Link
H
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002490:Central Nervous System / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008297:Male; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma