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

S Meehan1, A J Wu, E C Kang

  • 1Secretory Physiology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.

The American Journal of Physiology
|January 22, 1998
PubMed

Insights

Interferon-gamma (IFN-gamma) reduces the calcium pump (SERCA) in human salivary cells, leading to depleted calcium stores and inhibited cell growth. Removing IFN-gamma reverses these effects, suggesting a novel growth inhibition mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) affect cell proliferation and calcium (Ca2+) homeostasis.
  • Previous studies showed these cytokines deplete intracellular Ca2+ stores in human submandibular ductal (HSG) cells.
  • The mechanism behind IFN-gamma-induced Ca2+ store depletion remained unclear.

Purpose of the Study:

  • To investigate the mechanism of IFN-gamma-induced intracellular Ca2+ store depletion in HSG cells.
  • To determine the role of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) in this process.

Main Methods:

  • HSG cells were treated with IFN-gamma +/- TNF-alpha.
  • Intracellular Ca2+ stores were assessed by measuring thapsigargin-dependent Ca2+ release.
  • SERCA protein levels were quantified using Western blotting with a SERCA2 antibody.
  • Antiproliferative effects were induced by various agents to differentiate from cytokine effects.

Main Results:

  • IFN-gamma +/- TNF-alpha treatment caused a time-dependent decrease in intracellular Ca2+ store refilling.
  • A corresponding decrease in SERCA protein levels was observed in cells treated with IFN-gamma +/- TNF-alpha.
  • TNF-alpha alone did not affect SERCA levels or Ca2+ stores.
  • Removal of cytokines restored cell growth, Ca2+ stores, and SERCA protein levels.
  • Other antiproliferative agents did not decrease SERCA levels, indicating specificity of the cytokine effect.

Conclusions:

  • IFN-gamma-induced decrease in SERCA protein levels is responsible for the depletion of intracellular Ca2+ stores in HSG cells.
  • This reduction in SERCA activity represents a novel mechanism for IFN-gamma-mediated inhibition of HSG cell growth.

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