title: Kirsten sarcoma virus-immortalized mast cell lines. Reversible inhibition of growth by dexamethasone and evidence for the presence of an autocrine growth factor.
abstract: Expansion of mast cell numbers occurs in vivo during certain inflammatory reactions, including active fibrosis, parasite infestations, and immediate hypersensitivity reactions. T cell-produced cytokines, including IL-3 and IL-4, are thought to control this mast cell proliferation in part, and glucocorticoid regulation of T cell-produced cytokines is thought to account for diminished mast cell proliferation during administration of glucocorticoids in vivo. Here we show that glucocorticoids have a direct inhibitory effect on proliferation of Kirsten sarcoma virus-immortalized mast cells (KiSV-MC) in vitro, with an ID50 of 1.0 +/- 0.2 nM dexamethasone (mean +/- SD, n = 4). At 10 nM dexamethasone, KiSV-MC proliferation was inhibited by 83 +/- 5% (mean +/- SD, n = 4). As determined by trypan blue staining and [3H]TdR incorporation, the glucocorticoid-mediated growth inhibition was due to diminished mast cell proliferation rather than cell death and was completely reversible after 6 days of glucocorticoid treatment. By cell cycle analysis, glucocorticoids diminished the percentage of mast cells in S phase and increased the percentage in G0-G1 phase. Although we show that the KiSV-MC proliferate via an autocrine mechanism, glucocorticoid treatment of the KiSV-MC did not inhibit their production of the autocrine growth factor. During 6 days of treatment with 1 to 1000 nM dexamethasone, mast cell carboxypeptidase activity increased by a maximum of 3.5-fold. In contrast, total chymotryptic and tryptic esterase activities diminished by as much as 40% with dexamethasone treatment. We conclude that glucocorticoids directly affect mast cell growth and differentiation at levels equal to the reported Kd for glucocorticoid receptors on other immune cells.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: E
authors.initials: E
authors.lastname: Tchekneva
authors.forename: W E
authors.initials: WE
authors.lastname: Serafin
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000494:pharmacology*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D007708:Kirsten murine sarcoma virus; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D006133:Growth Substances; D012333:RNA, Messenger; D015735:Mifepristone; D003907:Dexamethasone; D010450:Endopeptidases