Interferon-g induces a decrease in the intracellular calcium pump in a human salivary gland cell line

Meehan, Sean, Ava J. Wu, Elaine C. Kang, Takayuki Sakai, and Indu S. Ambudkar. Interferon-g induces a decrease in the intracellular calcium pump in a human salivary gland cell line. Am. J. Physiol. 273 (Cell Physiol. 42): C2030–C2036, 1997.—Interferon-g (IFN-g) 6 tumor necrosis factor-a (TNF-a) induces antiproliferation and intracellular Ca21 store depletion in a human submandibular ductal cell line (HSG), which can be reversed on cytokine removal [A. J. Wu, G. C. Chen, B. J. Baum, and I. S. Ambudkar. Am. J. Physiol. 270 (Cell Physiol. 39): C514–C521, 1996]. Here we have examined a possible mechanism for the IFN-g-induced intracellular Ca21 store depletion. There was a timedependent decrease in thapsigargin-dependent internal Ca21 release after exposure of the cells to the cytokines. The intracellular Ca21 pump [sarco(endo)plasmic reticulum Ca21ATPase (SERCA)] protein in lysates and membranes of cells treated with IFN-g 6 TNF-a, but not with TNF-a alone, showed a similar time-dependent decrease (examined using a SERCA2 antibody). Removal of the cytokines, which resulted in recovery of cell growth and refill of internal Ca21 stores, also increased the level of SERCA protein. The decrease in SERCA is not a result of decreased cell proliferation, since thapsigargin, 2,5-di-(t-butyl)-1,4-hydroquinone, or serumfree growth conditions induced antiproliferative effects on HSG cells without any corresponding decrease in SERCA. We suggest that the IFN-g-induced decrease in the level of SERCA accounts for the depleted state of internal Ca21 stores in cytokine-treated HSG cells. These data suggest a novel mechanism for the inhibition of HSG cell growth by IFN-g.