Author(s): Figueiredo, Florêncio ; Uhing, Ronald J. ; Kenji, Okonogi ; Gettys, Tom W. ; Johnson, Stewart P. ; Adams, Dolph O ; Prpic, Verônica
Date: 2016
Persistent ID: http://hdl.handle.net/123456789/202
Origin: Oasisbr
Subject(s): Ciências da saúde; Medicina; Patologia clínica
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The ability of interferon-gamma (IFN gamma) to increase class II major histocompatibility complex (class II MHC) gene products in murine macrophages involves activation of Na+/H+ exchange (Prpic V., Yu, S. F., Figueiredo, F., Hollenbach, P. W., Gawdi, G., Herman, B., Uhing, R. J., and Adams, D. O. (1989) Science 244, 469-471). The ability of IFN gamma to increase class II MHC gene product expression is inhibited by a variety of agents. In the present studies, the involvement of cAMP-dependent protein kinase in modulating IFN gamma-induced expression of MHC gene products and the mechanism of regulation were assessed in macrophages treated with agents which activated cAMP-dependent protein kinase by different molecular mechanisms. Prostaglandin E2 (PGE2) produced a rapid (within 30 s) dose-dependent elevation of cAMP which was paralleled by the activation of cAMP-dependent protein kinase. The elevation of cAMP by PGE2 was still evident at 1 h and maintained through a 4-h incubation. Concentrations of PGE2 which activated the protein kinase produced a dose-dependent inhibition of surface expression of I-A and transcription of class II MHC genes. Inhibition of IFN gamma-induced class II MHC gene product expression was also observed in macrophages treated with agents which activated cAMP-dependent protein kinase by postreceptor mechanisms. Dibutyryl-cAMP (0.01-1 mM), 25 microM forskolin, 0.1 micrograms/ml cholera toxin, and 3-isobutyl-1-methylxanthine (0.1-1 mM) each suppressed IFN gamma-induced cell surface I-A expression, class II MHC gene transcription, and 22Na+ influx. The results are consistent with the suggestion that activation of cAMP-dependent protein kinase regulates an early transductional event initiated by IFN gamma, perhaps Na+/H+ exchange, which is involved in regulating transcription of class II MHC genes and their subsequent expression.
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