title: Dipeptidyl peptidase-4 is highly expressed in bronchial epithelial cells of untreated asthma and it increases cell proliferation along with fibronectin production in airway constitutive cells.
abstract: BACKGROUND
  Type 2 helper T-cell cytokines including IL-13 play a central role in the pathogenesis of bronchial asthma (BA). During the course of our research, our attention was drawn to dipeptidyl peptidase-4 (DPP4) as one of the molecules that were induced from bronchial epithelial cells (BECs) by IL-13 stimulation. DPP4 could become a new biomarker or therapeutic target. The aim of this study was to investigate the expression of DPP4 in the asthmatic airway, and its role in the pathophysiology of asthma.
  
  
  METHODS
  BECs were isolated from patients with inhaled corticosteroid-treated asthma (stBA) and inhaled corticosteroid-naïve asthma (snBA) using bronchoscopy. DPP4 mRNA expression in freshly isolated BECs and primary cultured BECs with or without IL-13 stimulation was investigated by microarray analysis and quantitative real-time PCR (qPCR). The distribution of DPP4 protein was determined by immunostaining of transbronchial lung biopsy specimens from asthma patients. The effect of recombinant human (rh) DPP4 on the proliferation of lung fibroblasts (HFL-1) and bronchial smooth muscle cells (BSMCs) was examined, as well as its effect on the production of fibronectin (FN).
  
  
  RESULTS
  DPP4 mRNA was strongly expressed in freshly isolated BECs in snBA, and its expression was significantly enhanced by IL-13 stimulation. DPP4 mRNA expression in BECs of snBA significantly correlated with exhaled nitric oxide. Biopsied tissues of the asthmatic airway revealed strong expression of DPP4 protein in BECs from snBA subjects. rhDPP4 stimulated the proliferation of HFL-1 and BSMCs, and it also enhanced production of FN from these airway cells.
  
  
  CONCLUSIONS
  DPP4 may be involved in the pathologic features of asthmatic airway inflammation and cell proliferation and FN production.
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Shiobara
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan. kchibana@dokkyomed.ac.jp.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Chibana
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Arai
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Horigane
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Yumeko
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takemasa
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi Mibumachi, Shimotsugagun, Tochigi, 321-0293, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ishii
mesh_terms: D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D005353:Fibronectins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Bronchial asthma; Bronchial epithelial cells; Dipeptidyl peptidase-4; IL-13