title: Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells.
abstract: BACKGROUND
  Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells.
  
  
  METHODS
  HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-1β (IL-1β) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction.
  
  
  RESULTS
  IL-1β significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and 1,25(OH)2D.
  
  
  CONCLUSIONS
  Vitamin D, 25(OH)D, and 1,25(OH)2D play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-1β stimulated MMP-9 production and conversion to its active form but also inhibiting IL-1β inhibition on TIMP-1 and TIMP-2 production.
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Seo Hwa
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Moon Seong
authors.initials: MS
authors.lastname: Baek
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Dong Sik
authors.initials: DS
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Jong Seol
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Byoung Wook
authors.initials: BW
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Byoung Su
authors.initials: BS
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Jinkyeong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine, Gunpo, Korea.
authors.forename: Hui Jung
authors.initials: HJ
authors.lastname: Kim
keywords: Fibroblasts; Matrix Metalloproteinase 9; Vitamin D