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IL-1 induced release of Ca2+ from internal stores is dependent on cell-matrix interactions and regulates ERK

Qin Wang1, Gregory P Downey, Christine Choi

  • 1CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Ontario M5S 3E2, Canada.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|October 2, 2003
PubMed

Insights

Focal adhesions, crucial for cell-matrix interactions, regulate interleukin-1 (IL-1) signaling by controlling intracellular calcium (Ca2+) release and entry. This calcium signaling is essential for IL-1-induced ERK activation in fibroblasts.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Interleukin-1 (IL-1) signaling pathways are critical in cellular responses but the precise mechanisms modulating them remain unclear.
  • Cell-matrix adhesions, specifically focal adhesions, are known to influence IL-1 receptor localization and signaling.
  • Understanding how these adhesions impact IL-1-induced cellular events is essential for deciphering fibroblast behavior.

Purpose of the Study:

  • To investigate the role of focal adhesions in modulating intracellular calcium (Ca2+) handling during IL-1 signaling.
  • To elucidate the mechanisms by which focal adhesions affect IL-1-induced Ca2+ signals and ERK activation in human gingival fibroblasts.

Main Methods:

  • Human gingival fibroblasts were cultured on poly-l-lysine or fibronectin-coated surfaces.
  • Focal adhesion formation was inhibited using tenascin, Hep-I, or SPARC peptides.
  • Cellular Ca2+ handling was assessed following IL-1 or thapsigargin stimulation.
  • ERK activation was measured in response to IL-1 treatment.

Main Results:

  • Inhibition of focal adhesion formation blocked IL-1 and thapsigargin-induced Ca2+ release from the endoplasmic reticulum.
  • Focal adhesions were found to be essential for Ca2+ influx through store-operated channels.
  • Disruption of focal adhesions impaired IL-1-induced extracellular signal-regulated kinase (ERK) activation.

Conclusions:

  • Focal adhesions play a critical role in regulating both endoplasmic reticulum Ca2+ release and store-operated Ca2+ entry.
  • These adhesion-dependent Ca2+ signaling events are indispensable for IL-1-induced ERK activation in fibroblasts.
  • Extracellular matrix interactions and focal adhesion formation are key regulators of IL-1 signaling pathways.

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