IL-32 expression in the airway epithelial cells of patients with Mycobacterium avium complex lung disease
IL-32 expression in the airway epithelial cells of patients with Mycobacterium avium complex lung disease
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DOI：
10.1093/intimm/dxr075
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发表时间：
2011-11-01
影响因子：
4.4
通讯作者：
Chan, Edward D.
中科院分区：
文献类型：
--
作者：
Bai, Xiyuan;Ovrutsky, Alida R.;Chan, Edward D.
由鸟分枝杆菌复合体（MAC）引起的肺部疾病正在增加。更好地了解宿主对MAC生物的免疫反应将为开发针对这些难治性感染的新疗法提供基础。IL-32是一种新发现的促炎细胞因子，可增强宿主对多种微生物病原体的免疫力。诱导IL-32的细胞因子如干扰素- γ、IL-18、IL-12和肿瘤坏死因子- α对分枝杆菌免疫具有重要意义。我们进行了免疫组织化学和形态计量学分析，量化了11例MAC肺病患者和10例正常肺组织对照中IL-32的表达。基底膜长度正常化后，与对照组相比，mac感染肺气道上皮细胞中IL-32的表达显著增加。肺泡表面积正常化后，MAC患者肺ⅱ型肺泡细胞和肺泡巨噬细胞中IL-32表达有升高的趋势。感染M. avium的人气道上皮细胞（BEAS-2B）通过核因子κ b依赖机制产生IL-32。在BEAS-2B细胞和人单核细胞源性巨噬细胞中，外源性IL-32 γ显著降低细胞内鸟分枝杆菌的生长。从内源性IL-32表达沉默的THP-1单核细胞中恢复的细胞内鸟分枝杆菌数量增加证实了这一发现。IL-32的抗分枝杆菌作用可能部分是由于感染细胞的凋亡增加。这些发现表明，IL-32促进宿主对MAC生物的防御，但也可能有助于与MAC肺部疾病相关的气道炎症。
Lung disease due to Mycobacterium avium complex (MAC) organisms is increasing. A greater understanding of the host immune response to MAC organisms will provide a foundation to develop novel therapies for these recalcitrant infections. IL-32 is a newly described pro-inflammatory cytokine that enhances host immunity against various microbial pathogens. Cytokines that induce IL-32 such as interferon-gamma, IL-18, IL-12 and tumor necrosis factor-alpha are of considerable importance to mycobacterial immunity. We performed immunohistochemistry and morphometric analysis to quantify IL-32 expression in the lungs of 11 patients with MAC lung disease and 10 controls with normal lung tissues. After normalizing for basement membrane length, there was a profound increase in IL-32 expression in the airway epithelial cells of the MAC-infected lungs compared with controls. Following normalization for alveolar surface area, there was a trend toward increased IL-32 expression in type II alveolar cells and alveolar macrophages in the lungs of MAC patients. Human airway epithelial cells (BEAS-2B) infected with M. avium produced IL-32 by a nuclear factor-kappa B-dependent mechanism. In both BEAS-2B cells and human monocyte-derived macrophages, exogenous IL-32 gamma significantly reduced the growth of intracellular M. avium. This finding was corroborated by an increase in the number of intracellular M. avium recovered from THP-1 monocytes silenced for endogenous IL-32 expression. The anti-mycobacterial effect of IL-32 may be due, in part, to increased apoptosis of infected cells. These findings indicate that IL-32 facilitates host defense against MAC organisms but may also contribute to the airway inflammation associated with MAC pulmonary disease.