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Stat1 alpha expression is involved in IFN-gamma induction of the class II transactivator and class II MHC genes.
J Immunol. 1996 Aug 15; 157(4):1559-68.JI

Abstract

Class II MHC Ags are critical in the regulation of immune responses by presenting Ag to T lymphocytes, resulting in their activation and differentiation. Class II expression is rare in the normal central nervous system, but elevated expression on glial cells has been observed in several neurologic diseases. We have previously demonstrated that IFN-gamma-induced class II expression in glial cells involves activation of both tyrosine kinase and protein kinase C. IFN-gamma induces tyrosine phosphorylation of the tyrosine kinases Jak1 and Jak2 and of Stat1 alpha. In addition, IFN-gamma enhances expression of Stat1 alpha mRNA and protein. We utilized antisense oligonucleotides against Stat1 alpha to determine directly whether IFN-gamma-induced activation and/or enhancement of Stat1 alpha is involved in class II expression. Antisense oligonucleotides complementary to Stat1 alpha mRNA were introduced in CH235-MG astroglioma cells by transient transfection; such treatment inhibited both constitutive and IFN-gamma-enhanced expression of Stat1 alpha. IFN-gamma-induced class II MHC expression was also inhibited in cells exposed to Stat1 alpha antisense oligonucleotides. The fact that the class II promoter does not contain IFN-gamma-activated sequences for binding Stat1 alpha suggests that Stat1 alpha must activate another protein that is directly involved in class II expression. A likely candidate is the class II MHC transactivator (CIITA). IFN-gamma induction of CIITA mRNA was also inhibited in cells treated with antisense oligonucleotides against Stat1 alpha. These findings demonstrate that Stat1 alpha is involved in IFN-gamma induction of CIITA expression, resulting in class II MHC expression.

Authors+Show Affiliations

Department of Cell Biology, University of Alabama at Birmingham 35294, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8759739

Citation

Lee, Y J., and E N. Benveniste. "Stat1 Alpha Expression Is Involved in IFN-gamma Induction of the Class II Transactivator and Class II MHC Genes." Journal of Immunology (Baltimore, Md. : 1950), vol. 157, no. 4, 1996, pp. 1559-68.
Lee YJ, Benveniste EN. Stat1 alpha expression is involved in IFN-gamma induction of the class II transactivator and class II MHC genes. J Immunol. 1996;157(4):1559-68.
Lee, Y. J., & Benveniste, E. N. (1996). Stat1 alpha expression is involved in IFN-gamma induction of the class II transactivator and class II MHC genes. Journal of Immunology (Baltimore, Md. : 1950), 157(4), 1559-68.
Lee YJ, Benveniste EN. Stat1 Alpha Expression Is Involved in IFN-gamma Induction of the Class II Transactivator and Class II MHC Genes. J Immunol. 1996 Aug 15;157(4):1559-68. PubMed PMID: 8759739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stat1 alpha expression is involved in IFN-gamma induction of the class II transactivator and class II MHC genes. AU - Lee,Y J, AU - Benveniste,E N, PY - 1996/8/15/pubmed PY - 1996/8/15/medline PY - 1996/8/15/entrez SP - 1559 EP - 68 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 157 IS - 4 N2 - Class II MHC Ags are critical in the regulation of immune responses by presenting Ag to T lymphocytes, resulting in their activation and differentiation. Class II expression is rare in the normal central nervous system, but elevated expression on glial cells has been observed in several neurologic diseases. We have previously demonstrated that IFN-gamma-induced class II expression in glial cells involves activation of both tyrosine kinase and protein kinase C. IFN-gamma induces tyrosine phosphorylation of the tyrosine kinases Jak1 and Jak2 and of Stat1 alpha. In addition, IFN-gamma enhances expression of Stat1 alpha mRNA and protein. We utilized antisense oligonucleotides against Stat1 alpha to determine directly whether IFN-gamma-induced activation and/or enhancement of Stat1 alpha is involved in class II expression. Antisense oligonucleotides complementary to Stat1 alpha mRNA were introduced in CH235-MG astroglioma cells by transient transfection; such treatment inhibited both constitutive and IFN-gamma-enhanced expression of Stat1 alpha. IFN-gamma-induced class II MHC expression was also inhibited in cells exposed to Stat1 alpha antisense oligonucleotides. The fact that the class II promoter does not contain IFN-gamma-activated sequences for binding Stat1 alpha suggests that Stat1 alpha must activate another protein that is directly involved in class II expression. A likely candidate is the class II MHC transactivator (CIITA). IFN-gamma induction of CIITA mRNA was also inhibited in cells treated with antisense oligonucleotides against Stat1 alpha. These findings demonstrate that Stat1 alpha is involved in IFN-gamma induction of CIITA expression, resulting in class II MHC expression. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8759739/Stat1_alpha_expression_is_involved_in_IFN_gamma_induction_of_the_class_II_transactivator_and_class_II_MHC_genes_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=8759739 DB - PRIME DP - Unbound Medicine ER -