Li Xuelin, Wu Haiqiao, Chen Xia
Department of Geriatric, Chongqing Third People's Hospital, Chongqing 400014, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2014 Dec;39(12):1228-32. doi: 10.11817/j.issn.1672-7347.2014.12.002.
To investigate the effect of tumor necrosis factor-α converting enzyme (TACE) on mucous hypersecretion in inflammatory airway.
Mucous hypersecretion model of human lung adenocarcinoma cells A549 was induced by human neutrophil elastase (HNE), and TNF-α converting enzyme inhibitor-1 (TAPI-1), an inhibitor of TACE, was chosen for the inference study. The expression of MUC5AC and TACE was examined. Th e cells were divided into 5 groups: a negative control group, HNE1 (15 nmol/L) group, HNE2 (25 nmol/L) group, HNE3 (50 nmol/L) group and TAPI-1 group. RT-PCR was used to examine MUC5AC and TACE mRNA expression. The protein expression of TACE and MUC5AC was examined by Western blot and ELISA, respectively.
HNE induced the TACE and MUC5AC mRNA and protein expression in a dose-dependent manner. Compared with the control group, the increases were all significantly increased in the three dosages of HNE group (P< 0.01). The HNE-induced TACE and MUC5AC mRNA and protein expression were dramatically attenuated in the presence of TAPI-1, an inhibitor of TACE (P< 0.01).
TACE participated cell signalling pathway of airway mucous hypersecretion, and could down regulation the level of inflammation airway mucous hypersecretion.
探讨肿瘤坏死因子-α转换酶(TACE)对炎性气道黏液高分泌的影响。
用人中性粒细胞弹性蛋白酶(HNE)诱导人肺腺癌细胞A549黏液高分泌模型,并选用TACE抑制剂肿瘤坏死因子-α转换酶抑制剂-1(TAPI-1)进行干预研究。检测MUC5AC和TACE的表达。细胞分为5组:阴性对照组、HNE1(15 nmol/L)组、HNE2(25 nmol/L)组、HNE3(50 nmol/L)组和TAPI-1组。采用RT-PCR检测MUC5AC和TACE mRNA表达。分别用Western blot和ELISA检测TACE和MUC5AC的蛋白表达。
HNE呈剂量依赖性诱导TACE和MUC5AC mRNA及蛋白表达。与对照组相比,HNE三个剂量组的表达均显著增加(P<0.01)。在TACE抑制剂TAPI-1存在的情况下,HNE诱导的TACE和MUC5AC mRNA及蛋白表达显著减弱(P<0.01)。
TACE参与气道黏液高分泌的细胞信号通路,并可下调炎性气道黏液高分泌水平。