title: Inhibition of IL-13-induced periostin in airway epithelium attenuates cellular protein expression of MUC5AC.
abstract: Serum periostin is increased in asthma and serves as a surrogate marker for IL-13 activity in the lung. Serum levels of periostin are the most robust biomarker predicting a favourable response to the anti-IL-13 drug, lebrikizumab. We investigated the mechanisms of IL-13 stimulation of periostin, the polarized secretion of periostin and whether periostin would have a direct effect on mucin secretion by airway cells.
  
  
  
  Normal human bronchial epithelial (NHBE) cells were cultured at air-liquid interface (ALI) in the presence of IL-13, and we evaluated the effect of the specific inhibitors, leflunomide (Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) inhibitor) or PD98059 (MEK/extracellular regulated protein kinase (ERK) inhibitor), on periostin production. We examined MUC5AC secretion from NHBE cells exposed to recombinant human (rh) periostin or IL-13 in the presence and absence of OC-20, a periostin-neutralizing antibody.
  
  
  
  IL-13 induced periostin protein which was predominantly secreted towards the basal surface of the cells. Periostin production was much greater from goblet cells than ciliated cells (P < 0.001). Periostin production after exposure to IL-13 was attenuated by both leflunomide (P < 0.001) and PD98059 (P < 0.001). The addition of exogenous periostin modestly increased MUC5AC secretion (P < 0.01), but did not visibly change cell morphology. IL-13-induced MUC5AC secretion was attenuated by OC-20 (P < 0.01).
  
  
  
  Periostin production in differentiated airway cells is mediated by JAK/STAT6 and MEK/ERK pathways. Periostin secretion is much greater from immunologically active goblet cells. IL-13-driven mucin production is partially inhibited by OC-20.
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.|Department of Otorhinolaryngology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Suzaki
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kawano
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Komiya
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Akaba
authors.affiliation: Division of Physiology, School of Nursing and Rehabilitation Sciences, Showa University, Yokohama, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Asano
authors.affiliation: Nasal and Paranasal Sinus Disease and Allergy Institute, Tokyo General Hospital, Tokyo, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Suzaki
authors.affiliation: Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.affiliation: Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Rubin
mesh_terms: D001249:Asthma / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D020397:Goblet Cells / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D055271:Mucin 5AC / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D018793:Interleukin-13; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; C512835:POSTN protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human
keywords: MUC5AC; goblet cells; interleukin-13; mucin; periostin