Respiratory medicine

1532-30641222017JanRespiratory medicineRespir MedIncreased levels of prostaglandin E-major urinary metabolite (PGE-MUM) in chronic fibrosing interstitial pneumonia.435043-5010.1016/j.rmed.2016.11.017S0954-6111(16)30312-2Dysregulation 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.Copyright © 2016 Elsevier Ltd. All rights reserved.HorikiriTsugumiTDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.HaraHiromichiHDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. Electronic address: hirohara@jikei.ac.jp.SaitoNayutaNDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.ArayaJunJDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.TakasakaNaokiNDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.UtsumiHirofumiHDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.YanagisawaHaruhikoHDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.HashimotoMitsuoMDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.YoshiiYutakaYDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.WakuiHiroshiHDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.MinagawaShunsukeSDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.IshikawaTakeoTDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.ShimizuKenichiroKDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.NumataTakanoriTDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.ArihiroSeijiSDivision of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.KanekoYumiYDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.NakayamaKatsutoshiKDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.MatsuuraTomokazuTDepartment of Laboratory Medicine, Jikei University School of Medicine, Tokyo, Japan.MatsuuraMasaakiMGraduate School of Public Health, Teikyo University, Tokyo, Japan.FujiwaraMutsunoriMDepartment of Clinical Pathology, Japanese Red Cross Medical Center, Tokyo, Japan.OkayasuIsaoIDepartment of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.ItoSatoruSIDAC Theranostics Inc., The University of Tokyo Entrepreneur Plaza, Tokyo, Japan.KuwanoKazuyoshiKDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.engJournal ArticleResearch Support, Non-U.S. Gov't20161124