Asthma Research Today is a free monthly online journal that collates and summarizes the latest research about Asthma, including details on symptoms, diagnosis, treatment, causes, medications. | ||||||||
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Niflumic acid suppresses interleukin-13-induced asthma phenotypes.Nakano T, Inoue H, Fukuyama S, Matsumoto K, Matsumura M, Tsuda M, Matsumoto T, Aizawa H, Nakanishi Y Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. RATIONALE: Chloride channels have been implicated in the regulation of mucus production in epithelial cells. Expression of hCLCA1, a calcium-activated chloride channel, has been reported to be increased in the airway epithelium of patients with asthma. Interleukin (IL)-13 induces the cardinal features of bronchial asthma, and glucocorticoids are not sufficient to suppress IL-13-induced airway hyperresponsiveness or goblet cell hyperplasia. OBJECTIVES: We studied the effects of chloride channel inhibitors in IL-13-induced asthma. METHODS: The effects of niflumic acid (NA), a relatively specific blocker of calcium-activated chloride channel (CLCA), on goblet cell hyperplasia, eosinophil accumulation, and airway hyperresponsiveness were evaluated after IL-13 instillation into the airways. Because IL-13-dependent features rely on JAK/STAT6 signaling, the effect of NA on phosphorylation of JAK2 and STAT6 after IL-13 stimulation was examined in airway epithelial cells in vitro. The expression of the mCLCA family in mouse lung after IL-13 local administration in vivo was analyzed using reverse transcription-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Treatment with NA inhibited not only IL-13-induced goblet cell hyperplasia but also airway hyperresponsiveness and eosinophilic infiltration. NA suppressed the eotaxin levels in bronchoalveolar lavage fluids and overexpression of the MUC5AC gene, a marker of goblet cell hyperplasia, in the lung after IL-13 instillation. NA suppressed JAK2 activation, STAT6 activation, and eotaxin expression in epithelial cells. The expression of mCLCA3 (mouse homolog hCLCA1), but not that of other CLCA family members, was up-regulated by IL-13. CONCLUSIONS: These findings suggest that a chloride channel inhibitor can control IL-13-mediated airway features at least by suppressing JAK/STAT6 activation. Published 1 June 2006 in Am J Respir Crit Care Med, 173(11): 1216-21.
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