Document Detail


Niflumic acid inhibits goblet cell degranulation in a guinea pig asthma model.
MedLine Citation:
PMID:  22377526     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Mitsuko Kondo; Junko Nakata; Naoki Arai; Takehiro Izumo; Etsuko Tagaya; Kiyoshi Takeyama; Jun Tamaoki; Atsushi Nagai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Allergology international : official journal of the Japanese Society of Allergology     Volume:  61     ISSN:  1440-1592     ISO Abbreviation:  Allergol Int     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-01     Completed Date:  2012-06-26     Revised Date:  2012-10-04    
Medline Journal Info:
Nlm Unique ID:  9616296     Medline TA:  Allergol Int     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  133-42     Citation Subset:  IM    
Affiliation:
First Department of Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Asthma / immunology*,  pathology*
Bronchial Provocation Tests
Cell Degranulation / drug effects*
Disease Models, Animal
Goblet Cells / drug effects*,  immunology*,  pathology
Guinea Pigs
Humans
Male
Niflumic Acid / pharmacology*
Chemical
Reg. No./Substance:
4394-00-7/Niflumic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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