IL-1β enhances cell adhesion to degraded fibronectin

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.