Iwata Yasuhiro, Okamoto Masaki, Hoshino Tomoaki, Kitasato Yasuhiko, Sakazaki Yuki, Tajiri Morihiro, Matsunaga Kazuko, Azuma Koichi, Kawayama Tomotaka, Kinoshita Takashi, Imaoka Haruki, Fujimoto Kiminori, Kato Seiya, Yano Hirohisa, Aizawa Hisamichi
Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Intern Med. 2010;49(22):2393-400. doi: 10.2169/internalmedicine.49.4049. Epub 2010 Nov 15.
Oxidant stress is thought to be involved in the establishment of idiopathic interstitial pneumonia (IIP). Thioredoxin 1 (TRX1) plays a role as a strong antioxidant in vivo, suggesting that TRX1 may be involved in the pathogenesis of IIPs. However, there is no report on TRX1 levels in the sera of IIPs. In addition, TRX1 expression in the lungs of non-specific interstitial pneumonia (NSIP) and cryptogenic organizing pneumonia (COP) patients also has not been reported. Here, we investigated whether or not TRX1 levels are altered in the lungs and sera of patients with idiopathic pulmonary fibrosis (IPF), NSIP, and COP.
Immunohistochemical analysis was performed to examine the expression of TRX1. TRX1 levels in sera were measured using an ELISA kit.
TRX1 was expressed in the bronchiole-alveolar epithelium, especially with regenerative or metaplastic feature, and in alveolar macrophages in usual interstitial pneumonia (UIP) and fibrotic NSIP. TRX1 was weakly expressed in the lungs of cellular NSIP and COP. TRX1 producing cells in UIP (n=16), fibrotic NSIP (n=15), cellular NSIP (n=4), and COP (n=5) were significantly increased when compared to nonsmokers (n=7). TRX1 producing cells in UIP and fibrotic NSIP were significantly increased when compared to cellular NSIP and COP. TRX1 levels in the sera of the patients with IPF (n=32; 74.2 ± 7.5 ng/mL), fibrotic NSIP (n=7; 82.5 ± 18.4 ng/mL), cellular NSIP (n=3; 62.2 ± 3.2 ng/mL) and COP (n=17; 88.8 ± 19.7 ng/mL) were significantly higher than those of control subjects (n=74; 35.3 ± 2.7 ng/mL). Furthermore, TRX1 levels in the sera of IPF patients who later showed acute exacerbation (n=7; 106.6 ± 16.3 ng/mL) were significantly higher than those of IPF patients without acute exacerbation (n=25; 65.1 ± 7.6 ng/mL).
Overproduction of TRX1 in the lungs and sera may play an important role in the pathogenesis of IIPs.
氧化应激被认为与特发性间质性肺炎（IIP）的发病机制有关。硫氧还蛋白1（TRX1）在体内作为一种强大的抗氧化剂发挥作用，这表明TRX1可能参与IIP的发病过程。然而，尚无关于IIP患者血清中TRX1水平的报道。此外，非特异性间质性肺炎（NSIP）和隐源性机化性肺炎（COP）患者肺组织中TRX1的表达也未见报道。在此，我们研究了特发性肺纤维化（IPF）、NSIP和COP患者肺组织及血清中TRX1水平是否发生改变。
采用免疫组织化学分析检测TRX1的表达。使用酶联免疫吸附测定（ELISA）试剂盒检测血清中TRX1水平。
TRX1在细支气管肺泡上皮细胞中表达，尤其是具有再生或化生特征的细胞，以及在寻常型间质性肺炎（UIP）和纤维化型NSIP的肺泡巨噬细胞中表达。TRX1在细胞型NSIP和COP的肺组织中弱表达。与非吸烟者（n = 7）相比，UIP（n = 16）、纤维化型NSIP（n = 15）、细胞型NSIP（n = 4）和COP（n = 5）中产生TRX1的细胞显著增多。与细胞型NSIP和COP相比，UIP和纤维化型NSIP中产生TRX1的细胞显著增多。IPF患者（n = 32；74.2±7.5 ng/mL）、纤维化型NSIP患者（n = 7；82.5±18.4 ng/mL）、细胞型NSIP患者（n = 3；62.2±3.2 ng/mL）和COP患者（n = 17；88.8±19.7 ng/mL）血清中的TRX1水平显著高于对照组（n = 74；35.3±2.7 ng/mL）。此外，后来出现急性加重的IPF患者（n = 7；106.6±16.3 ng/mL）血清中的TRX1水平显著高于未出现急性加重的IPF患者（n = 25；65.1±7.6 ng/mL）。
肺组织和血清中TRX1的过度产生可能在IIP的发病机制中起重要作用。
