Induction of matrix metalloproteinase-1 by tumor necrosis factor-α is mediated by interleukin-6 in cultured fibroblasts of keratoconus

Abstract

Inflammatory molecules and matrix metalloproteinase (MMPs) have been found over-expressed in the tear film of patients with keratoconus. However, the mechanistic link between inflammatory molecules and MMPs in the pathogenesis of keratoconus remains still elusive. Therefore, we investigated the effect of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on MMP-1 expression and used IL-6 antibody (IL-6 Ab) to examine the role of IL-6 on TNF-α mediated regulation of MMP-1 in fibroblasts of normal cornea and keratoconus. Real-time polymerase chain reaction, Enzyme-linked immunosorbent assay, and Western blot data demonstrated that MMP-1 and IL-6 were expressed in fibroblasts of normal cornea and keratoconus. Levels of MMP-1 and IL-6 were significantly higher in keratoconus than normal cornea. TNF-α treatment led to a significant increase in IL-6 levels. IL-6 treatment induced MMP-1 synthesis in normal cornea and keratoconus. TNF-α increased MMP-1 expression in a dose- and time-dependent manner and this response was completely inhibited by the IL-6 Ab. In conclusion, these results indicate that fibroblasts of keratoconus shows increased levels of IL-6 and MMP-1 gene and protein expression and IL-6 mediates the TNF-α-induced MMP-1 expression.

Octenidine-based hydrogel shows anti-inflammatory and protease-inhibitory capacities in wounded human skin

“…The analysis revealed strong functional interaction between members of the MMP family (MMP1, 2, 3) and IL-6 (Fig. S3 ), conforming and extending studies demonstrating that IL-6 regulates tissue MMPs 35 , 36 .

Figure 2 OCT regulates proteins involved in wound healing and immune response.

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Matrix metalloproteinases in keratoconus – Too much of a good thing?

“…MMP-1 mRNA and protein expression in these cells 80 . MMP-9 mRNA, protein and overall activity levels in corneal epithelial cells in-vitro is stimulated by treatment with TGF-β, IL-1β and TNF-α 36,40,81 , and induction of both MMP-9 and MMP-1 mRNAs can be initiated by platelet-activating factor (PAF), an important inflammatory mediator which accumulates in the cornea following an injury 82 .…”

Exopolysaccharide from Lactobacillus plantarum HY7714 Protects against Skin Aging through Skin–Gut Axis Communication

“…According to recent studies, a few types of matrix metalloproteinase (MMP) play vital roles in the development of inflammation in intestinal epithelial cells. Multiple studies have reported that IL-1β and TNFα increase expression of MMP [ 39 , 40 ]. At the same time, MMPs play a role in promoting ECM degradation following UVB damage in skin dermis and epidermal cells.…”