PENTOXIFYLLINE-INDUCED AND CAFFEINE-INDUCED MODULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION ON MURINE TUMOR-CELL LINES

The methylxanthines, pentoxifylline (PTX) and caffeine, modulated majo r histocompatibility complex class I expression on three constitutivel y class I-positive murine T cell lymphoma lines. On two cell lines, PT X or caffeine treatment enhanced H-2K and H-2D expression. Treatment w ith PTX and either interferon-gamma, interferon-alpha/beta, tumor necr osis 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 e xpression and reduced K expression. Treatment with PTX and any of the cytokines resulted in a level of D expression greater than that seen f ollowing treatment with either PTX or cytokines alone. However, PTX in hibited the cytokine-induced enhancement of K expression. PTX and caff eine 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 caff eine-mediated enhancement of class I expression was at least partially blocked by an inhibitor of cAMP-dependent protein kinase A. These res ults demonstrate that PTX and caffeine are able to regulate class I ex pression and that this regulation involves a cAMP-dependent mechanism.