Interferon-γ inhibits collagen phagocytosis in human fibroblasts by inducing subcortical actin assembly and reducing ability of β1 integrin to bind to collagen

Objective: We investigated the possible roles of interferon-gamma (IFN-gamma) in modulation of extracellular and intracellular routes of collagen digestion by human fibroblasts. Methods: Human gingival fibroblasts were treated with IFN-gamma, after which matrix metalloproteinase-1 (MMP-1) activation was determined. Following the IFN-gamma treatment, cells were further incubated with either activating antibody for beta(1) integrin or actin monomer-sequestering agent latrunculin B before incubation with collagen-coated fluorescent beads. Thereafter, the binding and internalization of the beads were assessed. Results: IFN-gamma had no significant effect on MMP-1 activation, however, it reduced the binding of collagen-coated beads in the minimum affinity range and, subsequently, internalization of the beads. The inhibitory effects of IFN-gamma were partially reversed by adding either the beta, integrin activating antibody or latrunculin B. Conclusions: Although IFN-gamma does not appreciably moderate the extracellular route of collagen digestion by human fibroblasts, the reduced level of collagen phagocytosis by IFN-gamma in the cells may contribute to fibrosis in inflamed connective tissues. Further, IFN-gamma may decrease the binding of collagen and following phagocytosis in cells by inducing a subcortical actin assembly and reducing the ability of beta 1 integrin to bind to collagen.