IL-32 抑制血管生成：在哮喘中的可能作用。

Inhibition of angiogenesis by IL-32: possible role in asthma.

机构信息

Swiss Institute of Allergy and Asthma Research, Davos, Switzerland.

出版信息

J Allergy Clin Immunol. 2012 Apr;129(4):964-73.e7. doi: 10.1016/j.jaci.2011.12.1002. Epub 2012 Feb 14.

DOI:10.1016/j.jaci.2011.12.1002

PMID:22336080

Abstract

BACKGROUND

IL-32 is a proinflammatory cytokine involved in various chronic inflammatory diseases. Chronic airway inflammation in asthmatic patients results in structural airway changes, including angiogenesis. Vascular endothelial growth factor (VEGF) is a key inducer of angiogenesis in the airways of asthmatic patients.

OBJECTIVE

The aim of the study was to investigate the expression and function of IL-32 in patients with angiogenesis and asthma.

METHODS

The expression and regulation of IL-32 in normal human bronchial epithelial (NHBE) cells was analyzed by using RT-PCR, ELISA, Western blotting, immunofluorescent staining, and flow cytometry. After knockdown of IL-32 in NHBE cells by small interfering RNA (siRNA) transfections, VEGF secretion was quantified by means of ELISA. New blood vessel formation was determined with human umbilical vein endothelial cells by culturing with supernatants from IL-32 siRNA-transfected NHBE cells. IL-32 was determined in serum and induced sputum samples of asthmatic patients and healthy control subjects by means of ELISA.

RESULTS

IL-32 is expressed in NHBE cells on stimulation with IFN-γ, TNF-α, T(H)1 cells, and rhinovirus. Inhibition of IL-32 expression resulted in significantly increased secretion of the proangiogenic factors VEGF and platelet-derived growth factor by NHBE cells. Human umbilical vein endothelial cells cultured in supernatants from IL-32 siRNA-transfected NHBE cells showed enhanced in vitro angiogenesis. IL-32 is detectable in induced sputum from asthmatic patients. IL-32 serum levels were significantly higher in asthmatic patients compared with those seen in healthy control subjects and correlated with response to asthma treatment.

CONCLUSION

IL-32 is induced by IFN-γ, TNF-α, T(H)1 cells, and rhinovirus in bronchial epithelial cells. It inhibits angiogenesis, and its serum levels are associated with a good treatment response in asthmatic patients.

摘要

背景

IL-32 是一种参与多种慢性炎症性疾病的促炎细胞因子。哮喘患者的慢性气道炎症导致结构气道变化，包括血管生成。血管内皮生长因子（VEGF）是哮喘患者气道血管生成的关键诱导剂。

目的

本研究旨在探讨 IL-32 在伴有血管生成和哮喘的患者中的表达和功能。

方法

采用 RT-PCR、ELISA、Western blot、免疫荧光染色和流式细胞术分析正常人气道上皮（NHBE）细胞中 IL-32 的表达和调节。通过小干扰 RNA（siRNA）转染使 NHBE 细胞中 IL-32 沉默后，通过 ELISA 定量测定 VEGF 分泌。用 IL-32 siRNA 转染的 NHBE 细胞上清培养人脐静脉内皮细胞，确定新血管形成。通过 ELISA 测定哮喘患者和健康对照者血清和诱导痰样本中的 IL-32。

结果

IFN-γ、TNF-α、T(H)1 细胞和鼻病毒刺激可使 NHBE 细胞表达 IL-32。抑制 IL-32 表达可使 NHBE 细胞分泌的促血管生成因子 VEGF 和血小板衍生生长因子显著增加。用 IL-32 siRNA 转染的 NHBE 细胞上清培养的人脐静脉内皮细胞显示体外血管生成增强。可在哮喘患者的诱导痰中检测到 IL-32。与健康对照者相比，哮喘患者的 IL-32 血清水平明显升高，且与哮喘治疗反应相关。