INTERFERON-GAMMA INDUCES PERSISTENT DEPLETION OF INTERNAL CA2-GLAND CELL-LINE( STORES IN A HUMAN SALIVARY)

Interferon-gamma (IFN-gamma), in the presence of tumor necrosis factor -alpha (TNF-alpha), decreases proliferation of a human salivary gland ductal cell line, HSG (Wu, A., R. Kurrasch, J. Katz, P. Fox, B. Baum, and J. Atkinson. J. Cell. Physiol. 161: 217-226, 1994). We examined th e possible effects of these cytokines (1,000 U/ml IFN-gamma +/- 20 U/m l TNF-alpha for 7 days) on Ca2+ mobilization in HSG cells. In HSG cell s, fetal bovine serum (10%) or carbachol (100 mu M) stimulated rapid i ncreases in cytosolic Ca2+ concentration ([Ca2+](i)), apparently mobil ized from different thapsigargin-sensitive intracellular Ca2+ stores. Serum induced a proliferative effect; on HSG cells, which was suppress ed (>90%) by treatment with IFN-gamma +/- TNF-alpha, but not with TNF- alpha. alone. Serum-, carbachol-, and thapsigargin-stimulated [Ca2+](i ) elevations were reduced by 90, 60, and >65%, respectively, in cells treated with IFN-gamma +/- TNF-alpha and 30, 45, and 45%, respectively , in cells treated with TNF-alpha. Removal of the cytokines from the g rowth medium induced recovery of both cell proliferation and Ca2+ mobi lization responses within 7 days. Treatment of HSG cells with thapsiga rgin (0.02-2 nM) induced a dose-dependent decrease in cell proliferati on. Additionally, acute treatment (<10 min) of cells with LFN-gamma di d not affect [Ca2+](i) or alter carbachol-, thapsigargin-, or serum-in duced changes in [Ca2+](i). These data demonstrate that prolonged trea tment of HSG cells with IFN-gamma +/- TNF-alpha leads to a persistent depletion of intracellular Ca2+ stores. We suggest that this may have a role in cell growth.