Interferon-_ induces persistent depletion of intracellular ca2+
stores in a human salivary gland cell line.
Wu, Ava J., Zhi Jian Chen, Bruce J. Baum, and Indu S. Ambudkar.
Clinical Investigations and Patient Care Branch and Laboratory of
Oral Medicine, National Institute of Dental Research, National
Institutes of Health, Bethesda, MD 20892
APStracts 2:0311C, 1995.
The inflammatory cytokine interferon-_ (IFN-_), in the presence of
tumor necrosis factor-[alpha] (TNF-[alpha]), induces a strong
antiproliferative effect on a human salivary gland ductal cell line,
HSG, (Wu et al. 1994. J. Cell. Physiol. 161:217-226). In this study
we have examined the possible effects of cytokine-treatment (1000U/ml
IFN-_ +/- 20U/ml TNF-[alpha] for 7 days) on agonist-stimulated Ca2+
mobilization in HSG cells. In control HSG cells, fetal bovine serum
(serum, 10%) or carbachol (100[mu]M) stimulated rapid increases in
cytosolic [Ca2+] ([Ca2+]i), apparently mobilized from different,
thapsigargin-sensitive, intracellular Ca2+ stores. Serum-, carbachol
-, and thapsigargin- stimulated [Ca2+]i elevations were reduced by
90%, 60%, and >65%, respectively, in cells treated with IFN-_
+/- TNF-[alpha]. Serum induced a dose-dependent mitogenic effect on
HSG cells, which was suppressed (>90%) by treatment with IFN-_
or with IFN-_+TNF-[alpha], but not with TNF-[alpha] alone. Cells
treated with TNF-[alpha] displayed a 45% decrease in [Ca2+]i
responses to carbachol or thapsigargin but only a 30% decrease in the
response to serum. Removal of the cytokines from the growth medium
induced recovery of both cell proliferation and the Ca2+ mobilization
responses within 7 days. When HSG cells were treated with
thapsigargin (0.02nM-2nM) to deplete internal Ca2+ stores, there was
a dose-dependent decrease in cell proliferation. Additionally, acute
treatment (<10 min) of cells with IFN-_ did not induce any
changes in [Ca2+]i or alter carbachol-, thapsigargin-, or serum
-induced changes in [Ca2+]i. These data demonstrate that prolonged
treatment of HSG cells with IFN-_+/-TNF-[alpha] leads to a persistent
depletion of intracellular Ca2+ stores and decreased serum and
agonist-stimulated [Ca2+] mobilization. We suggest that these
cytokine-induced changes could alter the physiological function and
growth of HSG cells.
Received 19 May 1995; accepted in final form 18 August 1995.
APS Manuscript Number C292-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.