Effect of 1,25-(OH)2D3 (a vitamin D analogue) on passively sensitized human airway smooth muscle cells

Abstract

Background and objectives: 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 D3 (1,25-(OH)2D3) 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)2D3 on passively sensitized human bronchial (airway) smooth muscle cell (HASMC) proliferation and MMP-9 and ADAM33 expressions. Methods: The effect of 1,25-(OH)2D3 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) 2D3 effectively suppressed passively sensitized HASMC proliferation, proliferating cell nuclear antigen expression and G1/S transition in HASMCs passively sensitized with asthmatic serum. Further analysis showed that 1,25-(OH)2D3 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) 2D3 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) 2D3 in preventing and treating asthmatic airway remodelling. © 2007 The Authors.