Pentoxifylline- and caffeine-induced modulation of major histocompatibility complex class I expression on murine tumor cell lines.
The methylxanthines, pentoxifylline (PTX) and caffeine, modulated major histocompatibility complex class I expression on three constitutively class I-positive murine T cell lymphoma lines. On two cell lines, PTX or caffeine treatment enhanced H-2K and H-2D expression. Treatment with PTX and either interferon-gamma, interferon-alpha/beta, tumor necrosis factor, or lymphotoxin increased the levels of K and D expression above those observed following treatment with either PTX or cytokines alone. On the third cell line, PTX or caffeine treatment enhanced D expression and reduced K expression. Treatment with PTX and any of the cytokines resulted in a level of D expression greater than that seen following treatment with either PTX or cytokines alone. However, PTX inhibited the cytokine-induced enhancement of K expression. PTX and caffeine did not induce class I expression on three constitutively class I-negative murine T cell lymphoma lines. Dibutyryl cAMP modulated class I expression in the same manner as PTX and caffeine. The PTX- and caffeine-mediated enhancement of class I expression was at least partially blocked by an inhibitor of cAMP-dependent protein kinase A. These results demonstrate that PTX and caffeine are able to regulate class I expression and that this regulation involves a cAMP-dependent mechanism.
Graduate Group in Immunology, University of Pennsylvania, Philadelphia 19104.
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Rosenthal
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D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000187:drug effects*; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D016399:Lymphoma, T-Cell; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D002110:Caffeine; D003994:Bucladesine; D016899:Interferon-beta; D007371:Interferon-gamma; D010431:Pentoxifylline