Taima Kageaki, Imaizumi Tadaatsu, Yamashita Koji, Ishikawa Akira, Fujita Takashi, Yoshida Hidemi, Takanashi Shingo, Okumura Ken, Satoh Kei
Second Department of Internal Medicine, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan.
Respiration. 2006;73(3):360-4. doi: 10.1159/000091646. Epub 2006 Feb 15.
Interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10/CXCL10) is a potent chemoattractant for activated T and NK cells, and elevated levels of IP-10 are identified in bronchoalveolar lavage fluids from patients with pulmonary disorders related to Th-1-type immunity, which is a prerequisite for elimination of viral pathogens. Bronchial epithelial cells play an important role in respiratory infections as the initiator of airway inflammation by releasing chemokines and expressing cell surface membrane molecules involved in leukocyte adhesion. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA) and induces antiviral reactions in cells.
We investigated the regulation of IP-10 in BEAS-2B bronchial epithelial cells in response to poly IC, and also addressed the possible role of retinoic-acid-inducible gene-I (RIG-I) and IFN-regulatory factor 3 (IRF-3), two genes involved in the signaling induced by viral infection.
The expressions of IP-10 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The overexpression of RIG-I or IRF-3 was performed by transfection of BEAS-2B cells with each cDNA.
Poly IC enhanced the expression of IP-10 mRNA and protein in concentration- and time-dependent manners. Overexpression of RIG-I or IRF-3 potentiated the poly-IC-induced upregulation of IP-10.
IP-10 may contribute to antiviral activity through the activation of Th-1-type immunity, and RIG-I and IRF-3 may be involved in this reaction.
10 kDa的干扰素(IFN)-γ诱导蛋白(IP-10/CXCL10)是活化T细胞和NK细胞的有效趋化因子,在与Th-1型免疫相关的肺部疾病患者的支气管肺泡灌洗液中发现IP-10水平升高,这是消除病毒病原体的先决条件。支气管上皮细胞作为气道炎症的启动者,通过释放趋化因子和表达参与白细胞黏附的细胞表面膜分子,在呼吸道感染中发挥重要作用。聚肌苷酸-聚胞苷酸(poly IC)是一种合成双链RNA(dsRNA),可诱导细胞产生抗病毒反应。
我们研究了BEAS-2B支气管上皮细胞中IP-10对poly IC的反应调节,并探讨了维甲酸诱导基因-I(RIG-I)和IFN调节因子3(IRF-3)这两个参与病毒感染诱导信号传导的基因的可能作用。
通过逆转录-聚合酶链反应和酶联免疫吸附测定分析IP-10 mRNA和蛋白的表达。通过用每个cDNA转染BEAS-2B细胞来实现RIG-I或IRF-3的过表达。
poly IC以浓度和时间依赖性方式增强IP-10 mRNA和蛋白的表达。RIG-I或IRF-3的过表达增强了poly IC诱导的IP-10上调。
IP-10可能通过激活Th-1型免疫来促进抗病毒活性,并且RIG-I和IRF-3可能参与此反应。