关键词: ADAM33，IL-4，NF-κB，TGF-β1，气道重塑

Abstract: Objective To investigate the influence of a disintegrin and matrix metalloprotease 33 (ADAM33) to the expression of nuclear factor-kappa B(NF-κB) and transforming growth factor-β1(TGF-β1) in interleukin-4 (IL-4)-stimulated human airway smooth muscle cells (HASMCs),and to provide a new theoretical basis for further improve the pathogenesis of asthma. Methods 50 μg/L IL-4 stimulated HASMCs for 24 hours, and the unstimulated cells were used as the control group, real-time quantitative PCR and Western blot were used to detect the expression of ADAM33.ADAM33-siRNA was transiently transfected into HASMCs after IL-4 stimulated HASMCs for 24 hours, real-time quantitative PCR and Western blot were respectively used to detect inhibition rates of ADAM33-siRNA and the expression of TGF-β1 and NF-κB at the mRNA level and the protein level. Results 50 μg/L IL-4 group was significantly promoting the expression of ADAM33 in HASMCs compared with the control group(P <0.05), the expression of ADAM33 at the mRNA level increased by approximately 4.36 times, and the protein level increased by approximately 3.3 times; ADAM33-siRNA-575 significantly inhibited the expression of ADAM33 in HASMCs;The relative expression of TGF-β1 mRNA in interference group, negative control group and blank control group were 0.602±0.024,1.01±0.176 and 1.239±0.171, respectively;the relative expression of NF-κB mRNA were 0.54±0.08,1.014±0.21 and 1.049±0.378,respectively; the relative expression of TGF-β1 protein were 0.227±0.016,0.7±0.048 and 0.715±0.025,and the relative expression of NF-κB protein were 0.335 ±0.048,0.922±0.04 and 0.943±0.046,respectively.Both at the mRNA level and the protein level, the expression of TGF-β1 and NF-κB in the interference group were significantly lower than those in the negative control group or in blank control group (P <0.05). Conclusions ADAM33 may be a key mediator in IL-4/NF-κB/TGF-β1 signaling pathway in HASMCs, and is expected to become an important target for prevention and treatment of asthma.

Key words: ADAM33, IL-4, NF-κB, TGF-β1,airway remodeling