Interferon-gamma inhibits collagen phagocytosis in human fibroblasts by inducing subcortical actin assembly and reducing ability of beta1 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 beta1 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 beta1 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 beta1 integrin to bind to collagen.
Takaki
T
T
Department of Periodontology, Showa University Dental School, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo 145-8515, Japan.
Kobayashi
M
M
Okubo
K
K
Takahashi
N
N
Okamatsu
Y
Y
Mochizuki
S
S
Yamamoto
M
M
Hasegawa
K
K
D000199:Actins / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1; D007371:Interferon-gamma / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects
D000199:Actins; D019012:Integrin beta1; D007371:Interferon-gamma; D003094:Collagen