Effect of 1,25-(OH)2D3 (a vitamin D analogue) on passively sensitized human airway smooth muscle cells.
OBJECTIVE
In asthma, airway smooth muscle cell (ASMC) hyperplasia plays an important role in airway remodelling. Increased expression of matrix metalloproteinases-9 (MMP-9), a disintegrin and metalloprotease 33 (ADAM33) in ASMCs are also relevant to asthmatic airway remodelling. 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) has potent antiproliferative properties in vitro in various cell types; however, its role in ASMCs is not well understood. This study investigated the effect of 1,25-(OH)(2)D(3) on passively sensitized human bronchial (airway) smooth muscle cell (HASMC) proliferation and MMP-9 and ADAM33 expressions.


METHODS
The effect of 1,25-(OH)(2)D(3) on cell proliferation was examined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium-bromide colorimetry assay; cell cycle analysis by flow cytometry; and immunocytochemical staining for proliferating cell nuclear antigen (PCNA). The expression of MMP-9 and ADAM33 in HASMCs was investigated by real-time quantitative PCR and Western Blot analysis.


RESULTS
1,25-(OH)(2)D(3) effectively suppressed passively sensitized HASMC proliferation, proliferating cell nuclear antigen expression and G(1)/S transition in HASMCs passively sensitized with asthmatic serum. Further analysis showed that 1,25-(OH)(2)D(3) significantly down-regulated the expressions of protein for MMP-9 and ADAM33, as well as their mRNA levels in passively sensitized HASMCs.


CONCLUSIONS
1,25-(OH)(2)D(3) has direct inhibitory effects on passively sensitized HASMCs in vitro, including inhibition of cell proliferation and expression of MMP-9 and ADAM33, suggesting a possible beneficial role for 1,25-(OH)(2)D(3) in preventing and treating asthmatic airway remodelling.
Song
Yingfang
Y
Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Qi
Haowen
H
Wu
Changgui
C
D051722:ADAM Proteins / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology*; D002117:Calcitriol / Q000031:analogs & derivatives*; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology*; D010101:Oxygen Consumption; D016133:Polymerase Chain Reaction
D051722:ADAM Proteins; C450441:ADAM33 protein, human; D020780:Matrix Metalloproteinase 9; D002117:Calcitriol