Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937
Shayo, C.; Davio, C.; Brodsky, A.; Mladovan, A.G.; Legnazzi, B.L.; Rivera, E.; Baldi, A.
Molecular Pharmacology 51(6): 983-990
1997
ISSN/ISBN: 0026-895X PMID: 9187264 Document Number: 483390
We examined the effects of histamine and its agonists on the expression of the c-fos and c-myc proto-oncogenes at the transcriptional and translational levels in the human promonocytic U937 call line. Histamine transiently increased cAMP and c-fos expression through H-2 receptors. Dibutyryl cAMP also increased c-fos mRNA and protein, and levels remained elevated even after 12 hr of treatment. Dose-dependence studies using histamine and dimaprit showed that the EC-50 values for cAMP production and c-fos increase were similar, suggesting that cAMP might be involved in c-fos induction via H-2 receptors. Furthermore, studies carried out using H7, a protein kinase A/protein kinase C inhibitor, blocked c-fos induction, whereas no effect was observed with bisindolylmaleimide, a specific protein kinase C inhibitor. No modification of c-myc expression could be detected on treatment with histamine or its analogues. Nevertheless, dibutyryl cAMP induced a down-regulation of the levels of this proto-oncogene. In addition, dibutyryl cAMP inhibited cell growth in a dose-dependent manner, whereas histamine failed to affect proliferation and differentiation of U937 cells. Cells pretreated with dimaprit showed a decrease in the cAMP response to subsequent addition of H-2 agonists, whereas the cAMP response to prostaglandin E-2 remained unaltered. This homologous mechanism of H-2 receptor desensitization was time dependent. These results indicate that histamine activates several mechanisms involved in the induction of differentiation, such as cAMP and c-fos production, but falls to promote differentiation of U937 cells, apparently due to the rapid desensitization of H-2 receptors.