Interleukin-10 Suppresses Proliferation and Remodeling of Extracellular Matrix of Cultured Human Skin Fibroblasts

Abstract

When we previously examined the participation of local expression of interleukin-10 (IL-10) and tumor necrosis factor-α (TNFα) in wound healing of an intestinal anastomosis under septic conditions in mice, we found that IL-10 and TNFα expressions were markedly enhanced around the anastomosis and that wound healing was impaired in this animal model. The purpose of the present study was to investigate the combined effect of IL-10 on proliferation and remodeling of the extracellular matrix (ECM) of cultured human skin fibroblasts. Human skin fibroblasts were cultured for 48 h with IL-10 and/or TNFα at various concentrations, then the proliferation rates were determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The concentration of transforming growth factor-β1 (TGFβ1) in cell culture supernatants was measured by enzyme-linked immunosorbent assay, and type I collagen protein and matrix metalloproteinase-I (MMP-I) were detected by indirect immunofluorescence in cultured cells incubated for 48 h with 10 ng/ml of IL-10 and/or 10 ng/ml of TNFα. IL-10 itself had no effect on fibroblast proliferation, but reduced TNFα-induced fibroblast proliferation. The concentration of TGFβ1 in cell culture supernatants was significantly lower in the presence of TNFα and IL-10 than in the presence of TNFα alone. Immunolabeling of fibroblasts for type I collagen protein was decreased in cells incubated with IL-10 and/or TNFα compared to controls. MMP-I immunolabeling was increased in cells incubated with IL-10, IL-10 and TNFα compared to control and cells incubated with TNFα. It is suggested that IL-10 is an inhibitory factor for the remodeling of the ECM during wound healing.

Inducible Costimulator (ICOS) and ICOS Ligand Signaling Has Pivotal Roles in Skin Wound Healing via Cytokine Production

“…26 By contrast, IL-10 is an inhibitory factor for the remodeling of extracellular matrix during wound healing. 40 Addition of a neutralizing anti-IL-10 Ab inhibits the infiltration of neutrophils and macrophages toward the wound. 41 Therefore, reduced IL-10 expression is not likely contributing to the delayed wound healing seen in mutant mice in the current study, although reduced cell infiltration may be partially induced by decreased IL-10 expression.…”

Immune-non Immune Networks in Intestinal Inflammation

“…In addition, stimulation with cytokines alters the proliferative response of intestinal myofibroblasts [42][43][44] and alters the phenotype. .…”

Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses

“…IL-10 reduces tumor necrosis factor-a (TNF-a)-induced proliferation of fibroblasts and decreases production of type 1 collagen and fibronectin by fibroblasts. 2,3 As mentioned before, the quantitative expression of IL-10 is highly heritable, and IL-10 genotypes contribute to this phenomenon. Indeed, the risk-conferring genotypes in Caucasians in this study-AA (À3575) and AA (À2763)-are strongly associated with low production of this cytokine.…”

“…1 Additionally, IL-10 modulates the extracellular matrix by inhibiting fibroblast proliferation and collagen production. 2,3 The interindividual differences in IL-10 production levels have a large genetic component. [4][5][6] Owing to these properties, there is a growing interest in determining the role of IL-10 genes in autoimmune diseases.…”