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Tuberculosis & Respiratory Diseases

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Vol.77 No.2
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Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2014, v.77 no.2, pp.73-80








& (2014). Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells. Tuberculosis & Respiratory Diseases, 77(2), 73-80.
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Abstract

Background: Low levels of serum vitamin D is associated with several lung diseases. The production and activationof matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of thecurrent study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 inhuman 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) for48 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-2mRNA 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 wassignificantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was alsosignificantly 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 woundrepair and tissue remodeling through not only inhibiting IL-1β stimulated MMP-9 production and conversion to its activeform but also inhibiting IL-1β inhibition on TIMP-1 and TIMP-2 production.

keywords
Vitamin D, Matrix Metalloproteinase 9, Fibroblasts

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