Horikiri Tsugumi, Hara Hiromichi, Saito Nayuta, Araya Jun, Takasaka Naoki, Utsumi Hirofumi, Yanagisawa Haruhiko, Hashimoto Mitsuo, Yoshii Yutaka, Wakui Hiroshi, Minagawa Shunsuke, Ishikawa Takeo, Shimizu Kenichiro, Numata Takanori, Arihiro Seiji, Kaneko Yumi, Nakayama Katsutoshi, Matsuura Tomokazu, Matsuura Masaaki, Fujiwara Mutsunori, Okayasu Isao, Ito Satoru, Kuwano Kazuyoshi
Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Respir Med. 2017 Jan;122:43-50. doi: 10.1016/j.rmed.2016.11.017. Epub 2016 Nov 24.
Dysregulation of the prostaglandin E2 (PGE2) signaling pathway has been implicated in interstitial pneumonia (IP) pathogenesis. Due to the unstable nature of PGE2, available detection methods may not precisely reflect PGE2 levels. We explored the clinical usefulness of measuring stable prostaglandin E-major urinary metabolite (PGE-MUM) with respect to pathogenesis and extent of chronic fibrosing IP (CFIP), including idiopathic pulmonary fibrosis (IPF), as PGE-MUM is reflective of systemic PGE2 production.
PGE-MUM was measured by radioimmunoassay in controls (n = 124) and patients with lung diseases (bronchial asthma (BA): n = 78, chronic obstructive pulmonary disease (COPD): n = 33, CFIP: n = 44). Extent of lung fibrosis was assessed by fibrosing score (FS) of computed tomography (CT) (FS1-4). Immunohistochemical evaluation of COX-2 was performed to find PGE2 producing cells in IPF. Human bronchial epithelial cells (HBEC) and lung fibroblasts (LFB) were used in in vitro experiments.
Compared to control, PGE-MUM levels were significantly elevated in CFIP. PGE-MUM levels were positively correlated with FS, and inversely correlated with %DLCO in IP (FS 1-3). COX-2 was highly expressed in metaplastic epithelial cells in IPF, but lower expression of EP2 receptor was demonstrated in LFB derived from IPF. TGF-β induced COX-2 expression in HBEC.
PGE-MUM, elevated in CFIP, is a promising biomarker reflecting disease activity. Metaplastic epithelial cells can be a source of elevated PGE-MUM in IPF.
前列腺素E2（PGE2）信号通路失调与间质性肺炎（IP）的发病机制有关。由于PGE2性质不稳定，现有的检测方法可能无法准确反映PGE2水平。我们探讨了测量稳定的前列腺素E - 主要尿代谢产物（PGE - MUM）对于慢性纤维化IP（CFIP）（包括特发性肺纤维化（IPF））发病机制和程度的临床实用性，因为PGE - MUM反映了全身PGE2的产生。
通过放射免疫分析法测量对照组（n = 124）和肺部疾病患者（支气管哮喘（BA）：n = 78，慢性阻塞性肺疾病（COPD）：n = 33，CFIP：n = 44）的PGE - MUM。通过计算机断层扫描（CT）的纤维化评分（FS）（FS1 - 4）评估肺纤维化程度。进行COX - 2的免疫组织化学评估以在IPF中找到产生PGE2的细胞。体外实验使用人支气管上皮细胞（HBEC）和肺成纤维细胞（LFB）。
与对照组相比，CFIP中PGE - MUM水平显著升高。PGE - MUM水平与FS呈正相关，与IP（FS 1 - 3）中的%DLCO呈负相关。COX - 2在IPF的化生上皮细胞中高表达，但在IPF来源的LFB中EP2受体表达较低。TGF - β诱导HBEC中COX - 2表达。
CFIP中升高的PGE - MUM是反映疾病活动的有前景的生物标志物。化生上皮细胞可能是IPF中PGE - MUM升高的来源。
