Niflumic acid and MSI-2216 reduce TNF-α-induced mucin expression in human airway mucosa

Hans Peter Hauber, Patrick Daigneault, Saul Frenkiel, Francois Lavigne, Hsiao Ling Hung, Roy C. Levitt, Qutayba Hamid

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Background: Human chloride channel, calcium-activated 1 (hCLCA1) has been shown to induce mucin (MUC) gene expression and mucus production in bronchial epithelial cells. Objective: To investigate whether blocking hCLCA1 decreases mucus production. Methods: Expression of hCLCA1 and mucus was stimulated with TNF-α in human upper airway mucosal explant tissue. MUC5AC mRNA and mucus protein expression was blocked by inhibiting hCLCA1 by using channel blockers (niflumic acid [NFA] and MSI-2216) without and with TNF-α stimulation. Expression of MUC5AC, hCLCA1, and COX-2 mRNA was quantified by using real-time PCR. Mucus protein was assessed by periodic acid Schiff staining. Laser capture microdissection was performed to quantify hCLCA1 and MUC5AC mRNA expression in epithelial cells derived from mucosal explant tissue. Results: TNF-α significantly increased MUC5AC and hCLCA1 mRNA as well as mucus and hCLCA1 protein expression in the mucosal explant tissue (P < .05). Inhibition of hCLCA1 with NFA or MSI-2216 showed a significant dose-dependent reduction of mucus production for both blockers in the mucosal explant tissue (P < .05). MUC5AC mRNA was also decreased by both blockers in the whole mucosal tissue and in laser-captured mucosa epithelial cells. Conclusions: Unstimulated and TNF-α-induced mucin expression could be decreased by NFA and MSI-2216. Inhibiting hCLCA1 may be a potential new approach to reduce mucus overproduction.

Original languageEnglish (US)
Pages (from-to)266-271
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume115
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

Keywords

  • Airway
  • Explant model
  • hCLCA1
  • Inhibition
  • Laser capture microdissection
  • MSI-2216
  • MUC5AC
  • Mucin
  • Niflumic acid
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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