title: 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.
authors.affiliation: 1 Shanxi Key Lab of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China.
authors.forename: Genlai
authors.initials: G
authors.lastname: Du
authors.affiliation: 2 Department of Biology, Taiyuan Normal University, Taiyuan 030031, China.
authors.forename: Chengxing
authors.initials: C
authors.lastname: Liu
authors.affiliation: 1 Shanxi Key Lab of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Li
authors.affiliation: 1 Shanxi Key Lab of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Chen
authors.affiliation: 3 Department of Excimer Laser, Shanxi Eye Hospital, Taiyuan 030002, China.
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.affiliation: 1 Shanxi Key Lab of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1 Shanxi Key Lab of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Feng
authors.affiliation: 1 Shanxi Key Lab of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Lan
mesh_terms: D000293:Adolescent; D000354:Africa, Western; D003315:Cornea / Q000378:metabolism / Q000503:physiopathology; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D007640:Keratoconus / Q000378:metabolism / Q000503:physiopathology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1
keywords: Corneal fibroblasts; inflammatory cytokine; keratoconus; matrix metalloproteinases (MMPs)