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IFN-gamma regulation of class II transactivator promoter IV in macrophages and microglia: involvement of the suppressors of cytokine signaling-1 protein.
J Immunol. 2001 Feb 15; 166(4):2260-9.JI

Abstract

The discovery of the class II transactivator (CIITA) transcription factor, and its IFN-gamma-activated promoter (promoter IV), have provided new opportunities to understand the molecular mechanisms of IFN-gamma-induced class II MHC expression. Here, we investigated the molecular regulation of IFN-gamma-induced murine CIITA promoter IV activity in microglia/macrophages. In the macrophage cell line RAW264.7, IFN-gamma inducibility of CIITA promoter IV is dependent on an IFN-gamma activation sequence (GAS) element and adjacent E-Box, and an IFN response factor (IRF) element, all within 196 bp of the transcription start site. In both RAW cells and the microglia cell line EOC20, two IFN-gamma-activated transcription factors, STAT-1alpha and IRF-1, bind the GAS and IRF elements, respectively. The E-Box binds upstream stimulating factor-1 (USF-1), a constitutively expressed transcription factor. Functionally, the GAS, E-Box, and IRF elements are each essential for IFN-gamma-induced CIITA promoter IV activity. The effects of the suppressors of cytokine signaling-1 (SOCS-1) protein on IFN-gamma-induced CIITA and class II MHC expression were examined. Ectopic expression of SOCS-1 inhibits IFN-gamma-induced activation of CIITA promoter IV and subsequent class II MHC protein expression. Interestingly, SOCS-1 inhibits the constitutive expression of STAT-1alpha and its IFN-gamma-induced tyrosine phosphorylation and binding to the GAS element in CIITA promoter IV. As well, IFN-gamma-induced expression of IRF-1 and its binding to the IRF element is inhibited. These results indicate that SOCS-1 may be responsible for attenuating IFN-gamma-induced CIITA and class II MHC expression in macrophages.

Authors+Show Affiliations

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

11160280

Citation

O'Keefe, G M., et al. "IFN-gamma Regulation of Class II Transactivator Promoter IV in Macrophages and Microglia: Involvement of the Suppressors of Cytokine Signaling-1 Protein." Journal of Immunology (Baltimore, Md. : 1950), vol. 166, no. 4, 2001, pp. 2260-9.
O'Keefe GM, Nguyen VT, Ping Tang LL, et al. IFN-gamma regulation of class II transactivator promoter IV in macrophages and microglia: involvement of the suppressors of cytokine signaling-1 protein. J Immunol. 2001;166(4):2260-9.
O'Keefe, G. M., Nguyen, V. T., Ping Tang, L. L., & Benveniste, E. N. (2001). IFN-gamma regulation of class II transactivator promoter IV in macrophages and microglia: involvement of the suppressors of cytokine signaling-1 protein. Journal of Immunology (Baltimore, Md. : 1950), 166(4), 2260-9.
O'Keefe GM, et al. IFN-gamma Regulation of Class II Transactivator Promoter IV in Macrophages and Microglia: Involvement of the Suppressors of Cytokine Signaling-1 Protein. J Immunol. 2001 Feb 15;166(4):2260-9. PubMed PMID: 11160280.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IFN-gamma regulation of class II transactivator promoter IV in macrophages and microglia: involvement of the suppressors of cytokine signaling-1 protein. AU - O'Keefe,G M, AU - Nguyen,V T, AU - Ping Tang,L L, AU - Benveniste,E N, PY - 2001/2/13/pubmed PY - 2001/4/21/medline PY - 2001/2/13/entrez SP - 2260 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 166 IS - 4 N2 - The discovery of the class II transactivator (CIITA) transcription factor, and its IFN-gamma-activated promoter (promoter IV), have provided new opportunities to understand the molecular mechanisms of IFN-gamma-induced class II MHC expression. Here, we investigated the molecular regulation of IFN-gamma-induced murine CIITA promoter IV activity in microglia/macrophages. In the macrophage cell line RAW264.7, IFN-gamma inducibility of CIITA promoter IV is dependent on an IFN-gamma activation sequence (GAS) element and adjacent E-Box, and an IFN response factor (IRF) element, all within 196 bp of the transcription start site. In both RAW cells and the microglia cell line EOC20, two IFN-gamma-activated transcription factors, STAT-1alpha and IRF-1, bind the GAS and IRF elements, respectively. The E-Box binds upstream stimulating factor-1 (USF-1), a constitutively expressed transcription factor. Functionally, the GAS, E-Box, and IRF elements are each essential for IFN-gamma-induced CIITA promoter IV activity. The effects of the suppressors of cytokine signaling-1 (SOCS-1) protein on IFN-gamma-induced CIITA and class II MHC expression were examined. Ectopic expression of SOCS-1 inhibits IFN-gamma-induced activation of CIITA promoter IV and subsequent class II MHC protein expression. Interestingly, SOCS-1 inhibits the constitutive expression of STAT-1alpha and its IFN-gamma-induced tyrosine phosphorylation and binding to the GAS element in CIITA promoter IV. As well, IFN-gamma-induced expression of IRF-1 and its binding to the IRF element is inhibited. These results indicate that SOCS-1 may be responsible for attenuating IFN-gamma-induced CIITA and class II MHC expression in macrophages. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11160280/IFN_gamma_regulation_of_class_II_transactivator_promoter_IV_in_macrophages_and_microglia:_involvement_of_the_suppressors_of_cytokine_signaling_1_protein_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11160280 DB - PRIME DP - Unbound Medicine ER -