Antibody to mCLCA3 suppresses symptoms in a mouse model of asthma.
Antibody to mCLCA3 suppresses symptoms in a mouse model of asthma.
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DOI：
10.1371/journal.pone.0082367
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Song L;Liu D;Wu C;Wu S;Yang J;Ren F;Li Y
哮喘是一种复杂的、异质性的慢性炎症性疾病，与粘液细胞化生和粘液高分泌有关。功能基因组分析表明，粘液细胞化生和粘液高分泌依赖于钙激活氯通道(CLCA)基因家族的成员。有报道称，抑制CLCA可以缓解哮喘症状。因此，mCLCA3抗体可能是治疗哮喘等过敏性疾病的一种有前途的策略。为了研究mCLCA3抗体的功能，我们构建了OVA诱导的慢性气道炎性疾病哮喘小鼠模型。采用HE染色检测大鼠气道炎症反应，PAS染色检测杯状细胞增殖和粘液高分泌，ELISA法检测支气管肺泡灌洗液中MUC5AC、IL-13、干扰素-γ水平，原位末端标记法和爱先蓝染色检测杯状细胞凋亡率，逆转录聚合酶链式反应、Western blotting和免疫组织化学方法检测mCLCA3、Bcl2和Bax的表达。在我们的研究中，与对照组和哮喘小鼠相比，接受mCLCA3抗体治疗的小鼠出现了较少的病理变化，包括显著减少了呼吸道炎症、杯状细胞数量和肺组织中mCLCA3的表达。BALF中MUC5AC和IL-13水平显著降低。我们还发现，经mCLCA3抗体处理后，杯状细胞凋亡率增加，同时伴有杯状细胞Bax水平的升高和Bcl2表达的降低。综上所述，我们的结果表明mCLCA3抗体有可能成为治疗哮喘的有效药物。
Asthma is a complex and heterogeneous chronic inflammatory disorder that is associated with mucous cell metaplasia and mucus hypersecretion. Functional genomic analysis indicates that mucous cell metaplasia and mucus hypersecretion depend on members of the calcium-activated chloride channel (CLCA) gene family. It has been reported that the inhibition of CLCAs could relieve the symptoms of asthma. Thus, the mCLCA3 antibody may be a promising strategy to treat allergic diseases such as asthma. We constructed asthmatic mouse models of OVA-induced chronic airway inflammatory disorder to study the function of the mCLCA3 antibody. Airway inflammation was measured by HE staining; goblet cell hyperplasia and mucus hypersecretion were detected by PAS staining; muc5ac, IL-13, IFN-γ levels in bronchoalveolar lavage fluid (BALF) were examined by ELISA; Goblet cell apoptosis was measured by TUNEL assay and alcian blue staining; mCLCA3, Bcl-2 and Bax expression were detected by RT-PCR, Western blotting and immunohistochemical analysis. In our study, mice treated with mCLCA3 antibody developed fewer pathological changes compared with control mice and asthmatic mice, including a remarkable reduction in airway inflammation, the number of goblet cells and mCLCA3 expression in lung tissue. The levels of muc5ac and IL-13 were significantly reduced in BALF. We also found that the rate of goblet cell apoptosis was increased after treatment with mCLCA3 antibody, which was accompanied by an increase in Bax levels and a decrease in Bcl-2 expression in goblet cells. Taken together, our results indicate that mCLCA3 antibody may have the potential as an effective pharmacotherapy for asthma.
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DOI：
10.1164/ajrccm.165.8.2107068
发表时间：
2002-04-15
影响因子：
24.7
作者：
Hoshino, M;Morita, S;Fujino, M
通讯作者：
Fujino, M
影响因子：
6.4
作者：
Groneberg, DA;Eynott, PR;Chung, KF
通讯作者：
Chung, KF
DOI：
10.1006/bbrc.1999.0168
发表时间：
1999-02-16
影响因子：
3.1
作者：
Komiya, T;Tanigawa, Y;Hirohashi, S
通讯作者：
Hirohashi, S
影响因子：
56.9
作者：
Antonsson, B;Conti, F;Martinou, JC
通讯作者：
Martinou, JC
影响因子：
3.2
作者：
Leverkoehne, I;Gruber, AD
通讯作者：
Gruber, AD