Pentoxifylline and other methyl xanthines inhibit interleukin-2 receptor expression in human lymphocytes.

Published

Journal Article

Addition of pentoxifylline to lymphocytes caused a dose-dependent decrease in PHA-induced interleukin-2 receptor (IL-2R) expression. Expression of IL-2R protein and mRNA were inhibited by 60% at a concentration of 1 mM. Pentoxifylline also inhibited release of IL-2R into the medium by 85%. Treatment with recombinant IL-2 (50 U/ml) did not abrogate the effect of pentoxifylline. In addition to inhibition of IL-2R expression, pentoxifylline also decreased the expression of transferrin receptors and class I MHC antigens. Pentoxifylline also inhibited cell proliferation. However, aphidicolin, an inhibitor of DNA polymerase alpha inhibited cell proliferation to the same extent as pentoxifylline, but had no effect on IL-2R expression, indicating that inhibition of cell proliferation does not necessarily lead to inhibition of IL-2R expression. The inhibitory effect on IL-2R expression was also noted with other methylxanthines, theophylline and isobutylmethylxanthine, and with dbcAMP and forskolin. The inhibitory activity of pentoxifylline was prevented by W-13, a calmodulin antagonist, but not by HA-1004, a cyclic AMP-dependent protein kinase inhibitor. This suggests that pentoxifylline might act in part through a Ca2+/calmodulin-dependent mechanism. Pentoxifylline and other methylxanthines may prove useful in delineating the biochemical pathways involved in induction and expression of cell surface receptors.

Full Text

Duke Authors

Cited Authors

  • Rao, KM; Currie, MS; McCachren, SS; Cohen, HJ

Published Date

  • July 1991

Published In

Volume / Issue

  • 135 / 2

Start / End Page

  • 314 - 325

PubMed ID

  • 1709825

Pubmed Central ID

  • 1709825

International Standard Serial Number (ISSN)

  • 0008-8749

Digital Object Identifier (DOI)

  • 10.1016/0008-8749(91)90276-h

Language

  • eng

Conference Location

  • Netherlands