TGF-beta suppression of IFN-gamma-induced class II MHC gene expression does not involve inhibition of phosphorylation of JAK1, JAK2, or signal transducers and activators of transcription, or modification of IFN-gamma enhanced factor X expression.
TGF-beta is a widely expressed immunoregulatory protein that exerts a diverse range of effects on many types of cells. One of the effects of TGF-beta is the inhibition of both constitutive and cytokine-inducible class II MHC gene expression. In this study, we demonstrate that TGF-beta inhibits expression of class II MHC surface protein, mRNA, and promoter activity in primary astrocytes, and that this inhibition is both dose and time dependent. TGF-beta does not act to inhibit IFN-gamma-induced gene expression in a global fashion, as induction of ICAM-1 and IRF-1 gene expression by IFN-gamma is unaffected by treatment with TGF-beta. Furthermore, TGF-beta does not affect events that are involved in IFN-gamma-induced intracellular signaling such as tyrosine phosphorylation of JAK1, JAK2, and STAT1 alpha, nor does it affect IFN-gamma induction of the class II X2 box binding protein IFN-gamma enhanced factor X. We speculate that TGF-beta may be exerting its effects by modulating the expression or function of constitutively expressed factors responsible for regulation of class II MHC gene expression in astrocytes.
Panek
R B
RB
Department of Cell Biology, University of Alabama at Birmingham 35294.
Lee
Y J
YJ
Benveniste
E N
EN
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000502:physiology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008969:Molecular Sequence Data; D009457:Neuroglia; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051381:Rats; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000502:physiology*
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507906:Jak1 protein, rat; C507927:Jak2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2