title: Niflumic acid inhibits goblet cell degranulation in a guinea pig asthma model.
abstract: BACKGROUND
  Human Ca(2+)-activated Cl ion channel 1 (hCLCA1) is expressed in goblet cell hyperplasia in the airway of asthmatics, and murine CLCA3 is associated with antigen-sensitized and IL-13-induced goblet cell metaplasia in mice. However, the role of CLCA in goblet cell degranulation is not fully investigated. Niflumic acid (NFA), a relatively specific CLCA inhibitor, inhibits goblet cell metaplasia, but the effect of NFA on goblet cell degranulation has not been determined in an asthma model.
  
  
  METHODS
  Guinea pigs were sensitized with ovalbumin (OA) twice and then challenged with saline, OA, histamine, and one of the Ca(2+)-dependent secretagogues, UTP. The PAS/AB-stained mucus area in the tracheal epithelium was measured with a computer image analysis system, and the morphology of mucus granules was examined by transmission electron microscopy. In the in vitro experiment, goblet cells cultured with IL-13 at the air-liquid interface were stimulated with UTP in the presence or absence of NFA, and the MUC5AC level in cell lysates was measured by ELISA.
  
  
  RESULTS
  The mucus areas were smaller in the OA-, histamine-, and UTP-challenged animals than in the saline-challenged animals. NFA inhibited the decrease in mucus area and morphological changes in mucus granules. UTP caused swelling and exocytosis of mucus granules and MUC5AC secretion by cultured goblet cells, and NFA inhibited these changes.
  
  
  CONCLUSIONS
  NFA inhibited the secretory response of mucus granules in an asthma model, suggesting that CLCA may be associated with goblet cell degranulation and that CLCA inhibitors may be useful for the treatment of hypersecretion in asthma.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Kondo
authors.forename: Junko
authors.initials: J
authors.lastname: Nakata
authors.forename: Naoki
authors.initials: N
authors.lastname: Arai
authors.forename: Takehiro
authors.initials: T
authors.lastname: Izumo
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tagaya
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Jun
authors.initials: J
authors.lastname: Tamaoki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001985:Bronchial Provocation Tests; D015550:Cell Degranulation / Q000187:drug effects*; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology*
chemical_list: D009544:Niflumic Acid