Huang Jian-Qiang, Chen Xiao-Yang, Huang Fang, Fan Ji-Min, Shi Xiao-Wei, Ju Yan-Kai
Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Respiratory Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Iran J Allergy Asthma Immunol. 2018 Feb;17(1):29-38.
Connexion 43 (Cx43), a gap junction protein, is expressed abundantly in the airway and has been implicated in the pathogenesis of asthma. However, the effects of blocking Cx43 in asthma remain unclear. We investigated the therapeutic effects of two specific Cx43 inhibitors (Gap26 and Gap27) on the development of allergic airway disease in mice. Allergic asthma was induced in BALB/c mice by sensitization and challenge with ovalbumin (OVA). Different doses of Cx43 inhibitors were administered by aerosol inhalation 1 h after OVA challenge on days 21 and 23. Airway hyperresponsiveness (AHR), lung pathology, mucus production, and inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were examined. We found that Gap26 significantly inhibited OVA-induced AHR, inflammatory cell infiltration surrounding the bronchia, mucus production, inflammatory cells and cytokines in BALF, and OVA-specific IgE in the serum in a dose-dependent manner. Gap27 showed effects similar to those of Gap26 in inhibiting inflammatory cytokine production in BALF. We conclude Cx43 inhibitor inhalation alleviates asthma featuresin mice and may be a promising therapy for clinical asthma.
连接蛋白43（Cx43）是一种间隙连接蛋白，在气道中大量表达，并与哮喘的发病机制有关。然而，阻断Cx43在哮喘中的作用仍不清楚。我们研究了两种特异性Cx43抑制剂（Gap26和Gap27）对小鼠过敏性气道疾病发展的治疗作用。通过用卵清蛋白（OVA）致敏和激发，在BALB/c小鼠中诱导过敏性哮喘。在第21天和第23天，在OVA激发后1小时通过气溶胶吸入给予不同剂量的Cx43抑制剂。检测气道高反应性（AHR）、肺病理学、黏液分泌以及支气管肺泡灌洗液（BALF）中的炎症细胞和细胞因子。我们发现，Gap26以剂量依赖的方式显著抑制OVA诱导的AHR、支气管周围的炎症细胞浸润、黏液分泌、BALF中的炎症细胞和细胞因子以及血清中的OVA特异性IgE。Gap27在抑制BALF中炎症细胞因子产生方面显示出与Gap26相似的作用。我们得出结论，吸入Cx43抑制剂可减轻小鼠的哮喘特征，可能是临床哮喘的一种有前景的治疗方法。
