title: IL-1β enhances cell adhesion to degraded fibronectin.
abstract: IL-1β is a prominent proinflammatory cytokine that mediates degradation of extracellular matrix proteins through increased expression of matrix metalloproteinases, which involves a signaling pathway in adherent cells that is restricted by focal adhesions. Currently, the mechanism by which IL-1β affects cell adhesion to matrix proteins is not defined, and it is not known whether degraded matrix proteins affect IL-1β signaling. We examined adhesion-related IL-1β signaling in fibroblasts attaching to native or MMP3-degraded fibronectin. IL-1β increased cell attachment, resistance to shear force and the numbers of focal adhesions containing activated β(1) integrins. IL-1β-enhanced attachment required FAK, kindlins 1/2, and talin. MMP3-degraded fibronectin-inhibited IL-1β-enhanced cell adhesion and promoted spontaneous ERK activation that was independent of IL-1β treatment. We conclude that IL-1β enhances the adhesion of anchorage-dependent cells to MMP3-degraded fibronectin, which, in turn, is associated with deregulated cellular responses to IL-1β. These data point to a novel role of IL-1β as a proadhesive signaling molecule in inflammation that employs kindlins and talin to regulate adhesion.
authors: Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
authors: Dhaarmini
authors: D
authors: Rajshankar
authors: Gregory P
authors: GP
authors: Downey
authors: Christopher A
authors: CA
authors: McCulloch
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005881:Gingiva / Q000166:cytology; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering; D015398:Signal Transduction; D016608:Talin / Q000235:genetics / Q000378:metabolism
chemical_list: C477322:FERMT3 protein, human; D005353:Fibronectins; D019012:Integrin beta1; D053583:Interleukin-1beta; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D016608:Talin; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse