Sun Xinrong, Chen Lu, Yan Wen
First Department of Respiratory Medicine, Xi'an Children's Hospital, Xi'an, China, 710003.
First Neonatal Department, Xi'an Children's Hospital, Xi'an, China, 710003.
Inflammation. 2017 Jun;40(3):770-777. doi: 10.1007/s10753-017-0521-9.
Childhood asthma, an airway inflammatory disease, is a serious threat to the child's quality of life. Recently, TIPE2 expression was reported to be decreased in children with asthma. Therefore, additional studies focusing on TIPE2 might provide an approach for treating childhood asthma. In this study, we found that TIPE2 was poorly expressed in hyperstretched human bronchial epithelial cells (BEAS-2B). TIPE2 overexpression also significantly suppressed the stretch-induced secretion of asthma-related inflammatory factors (TNF-α, TSLP, MMP-9, and VEGF). In contrast, TIPE2 inhibition significantly promoted the secretion of TNF-α, TSLP, MMP-9, and VEGF. Furthermore, overexpression of TIPE2 remarkably inhibited the activation of Wnt/β-catenin in hyperstretched BEAS-2B cells, while siTIPE2 activated Wnt/β-catenin in hyperstretched BEAS-2B cells. Further analysis showed that the Wnt/β-catenin signal inhibitor Dkk-1 could further enhance the TIPE2-induced suppression of Wnt/β-catenin signaling, which also suppressed the siTIPE2-induced secretion of TNF-α, TSLP, MMP-9, and VEGF in hyperstretched BEAS-2B cells. Dkk-1 reversed the effects of siRNA-TIPE2 on Wnt/β-catenin signaling and inflammatory cytokines. In summary, we have exhibited that TIPE2 inhibited the expression of asthma-related inflammatory factors in hyperstretched BEAS-2B cells by suppressing the Wnt/β-catenin signaling pathway. TIPE2 may be involved in airway inflammation during asthma attack, and it may be used as a potential therapeutic target for bronchial epithelial inflammation in childhood asthma.
儿童哮喘是一种气道炎症性疾病，严重威胁儿童的生活质量。最近有报道称，哮喘患儿中TIPE2表达降低。因此，针对TIPE2的进一步研究可能为治疗儿童哮喘提供一种方法。在本研究中，我们发现TIPE2在过度拉伸的人支气管上皮细胞（BEAS-2B）中表达较低。TIPE2过表达也显著抑制了拉伸诱导的哮喘相关炎症因子（TNF-α、TSLP、MMP-9和VEGF）的分泌。相反，TIPE2抑制显著促进了TNF-α、TSLP、MMP-9和VEGF的分泌。此外，TIPE2过表达显著抑制了过度拉伸的BEAS-2B细胞中Wnt/β-连环蛋白的激活，而siTIPE2则激活了过度拉伸的BEAS-2B细胞中的Wnt/β-连环蛋白。进一步分析表明，Wnt/β-连环蛋白信号抑制剂Dkk-1可进一步增强TIPE2诱导的Wnt/β-连环蛋白信号抑制，这也抑制了过度拉伸的BEAS-2B细胞中siTIPE2诱导的TNF-α、TSLP、MMP-9和VEGF的分泌。Dkk-1逆转了siRNA-TIPE2对Wnt/β-连环蛋白信号和炎性细胞因子的影响。总之，我们已经证明TIPE2通过抑制Wnt/β-连环蛋白信号通路抑制了过度拉伸的BEAS-2B细胞中哮喘相关炎症因子的表达。TIPE2可能参与哮喘发作期间的气道炎症，它可能作为儿童哮喘支气管上皮炎症的潜在治疗靶点。
