IL-1 induced release of Ca2+ from internal stores is dependent on cell-matrix interactions and regulates ERK activation.
The cellular mechanisms that modulate interleukin-1 (IL-1) signaling are not defined. In fibroblasts, IL-1 signaling is affected by the nature of cell-matrix adhesions including focal adhesions, adhesive domains that sequester IL-1 receptors. We conducted studies to elucidate which steps of cellular Ca2+ handling are affected by focal adhesions and by which mechanisms focal adhesions modulate IL-1-induced Ca2+ signals and ERK activation in human gingival fibroblasts. Cells were plated on poly-l-lysine or fibronectin and treated with tenascin, Hep-I, or SPARC peptides to inhibit focal adhesion formation. These treatments blocked IL-1 and thapsigargin-induced Ca2+ release from the endoplasmic reticulum, indicating that the ER-release pathway is focal adhesion dependent. Focal adhesions were also required for Ca2+ entry through store-operated channels and for IL-1-induced ERK activation. Thus interactions with the extracellular matrix and focal adhesion formation regulate IL-1-induced generation of intracellular Ca2+ signals that in turn are required for ERK activation.
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002448:Cell Adhesion; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology; D015676:Osteonectin / Q000494:pharmacology; D010766:Phosphorylation; D019063:Tenascin / Q000494:pharmacology
D015220:Calcium Channels; C110208:Hep I peptide; D007375:Interleukin-1; D009842:Oligopeptides; D015676:Osteonectin; D019063:Tenascin; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium