Tuberculosis and Respiratory Diseases

  • 제77권2호
  • /
  • Pages.73-80
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  • 2014
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  • 1738-3536(pISSN)
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  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
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Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells

  • Kim, Seo Hwa (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine) ;
  • Baek, Moon Seong (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine) ;
  • Yoon, Dong Sik (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine) ;
  • Park, Jong Seol (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine) ;
  • Yoon, Byoung Wook (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine) ;
  • Oh, Byoung Su (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine) ;
  • Park, Jinkyeong (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine) ;
  • Kim, Hui Jung (Department of Internal Medicine, Wonkwang University Sanbon Hospital, Wonkwang University College of Medicine)
  • 투고 : 2014.03.05
  • 심사 : 2014.06.23
  • 발행 : 2014.08.29
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초록

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-$1{\beta}$ (IL-$1{\beta}$) 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-$1{\beta}$ 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 $1,25(OH)_2D$. Conclusion: 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-$1{\beta}$ stimulated MMP-9 production and conversion to its active form but also inhibiting IL-$1{\beta}$ inhibition on TIMP-1 and TIMP-2 production.

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