Suppressive activity of vitamin D3 on matrix metalloproteinase production from cholesteatoma keratinocytes in vitro.
There is much evidence that degradation of the extracellular matrix is essential for the development of cholesteatomas and that this is induced by activation of matrix metalloproteinases (MMPs). Vitamin D3 (VD3) has several well-recognised biological activities, including suppression of MMP production. The present study, therefore, was undertaken to examine whether VD3 could suppress MMP production from cholesteatoma keratinocytes in vitro. Keratinocytes (2.5 x 10(5) cells/mL) induced from cholesteatoma tissue specimens were cultured with various concentrations of VD3. After one hour, lipopolysaccharide was added to the cell cultures at 100 mug/mL. The culture supernatants were then collected and assayed for MMP-1 and MMP-3 by ELISA. We also used ELISA to measure the levels of both TIMP (tissue inhibitor of metalloproteinase)-1 and TIMP-2 in culture supernatants. Addition of VD3 into keratinocyte cultures caused the suppression of MMP and TIMP production, which was increased by LPS stimulation. This was dose-dependent. The present results showing the suppressive activity of VD3 on the production of MMPs, which are responsible for tissue remodeling, strongly suggest that VD3 would be a good candidate for an agent in the medical treatment of, or prophylaxis for, cholesteatomas.
Kobayashi
Hitome
H
Department of Otorhinolaryngology, Showa University of Medicine, Tokyo, Japan. hitomek@med-showa-u.ac.jp
Asano
Kazuhito
K
Kanai
Ken-ichi
K
Suzaki
Harumi
H
D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology* / Q000627:therapeutic use; D002781:Cholesteatoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use
D019715:Tissue Inhibitor of Metalloproteinase-1; D014815:Vitamins; D019716:Tissue Inhibitor of Metalloproteinase-2; D002762:Cholecalciferol; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1