title: Increased levels of prostaglandin E-major urinary metabolite (PGE-MUM) in chronic fibrosing interstitial pneumonia.
abstract: 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.
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Horikiri
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. Electronic address: hirohara@jikei.ac.jp.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hara
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Nayuta
authors.initials: N
authors.lastname: Saito
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Araya
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takasaka
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Utsumi
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Yanagisawa
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshii
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakui
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Minagawa
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Numata
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Arihiro
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Laboratory Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsuura
authors.affiliation: Graduate School of Public Health, Teikyo University, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuura
authors.affiliation: Department of Clinical Pathology, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Okayasu
authors.affiliation: IDAC Theranostics Inc., The University of Tokyo Entrepreneur Plaza, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.affiliation: Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D007564:Japan / Q000453:epidemiology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000378:metabolism; D011466:Prostanoic Acids / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014556:Urine / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D011453:Prostaglandins; D011466:Prostanoic Acids; D016212:Transforming Growth Factor beta; C037830:11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: IPF; Interstitial pneumonia; PGE-MUM