Suppressive Activity of Vitamin D3 on Matrix Metalloproteinase Production From Cholesteatoma Keratinocytes In Vitro

摘要

There is much evidence that degradation of theextracellular matrix is essential for the development ofcholesteatomas and that this is induced by activation of matrixmetalloproteinases (MMPs). Vitamin D3 (VD3) has severalwell-recognised biological activities, including suppression of MMPproduction. The present study, therefore, was undertaken to examinewhether VD3 could suppress MMP production from cholesteatomakeratinocytes in vitro. Keratinocytes (2.5 × 105 cells/mL) induced from cholesteatoma tissue specimenswere cultured with various concentrations of VD3. After one hour,lipopolysaccharide was added to the cell cultures at 100 μg/mL. The culture supernatants were then collected andassayed for MMP-1 and MMP-3 by ELISA. We also used ELISA to measurethe levels of both TIMP (tissue inhibitor of metalloproteinase)-1and TIMP-2 in culture supernatants. Addition of VD3 intokeratinocyte cultures caused the suppression of MMP and TIMPproduction, which was increased by LPS stimulation. This wasdose-dependent. The present results showing the suppressiveactivity of VD3 on the production of MMPs, which are responsible fortissue remodeling, strongly suggest that VD3 would be a goodcandidate for an agent in the medical treatment of, or prophylaxisfor, cholesteatomas.