Cigarette smoke alters IL-33 expression and release in airway epithelial cells

Elisabetta Pace, Caterina Di Sano, Serafina Sciarrino, Valeria Scafidi, Maria Ferraro, Giuseppina Chiappara, Liboria Siena, Sebastiano Gangemi, Patrizio Vitulo, Antonino Giarratano, Mark Gjomarkaj

Research output: Contribution to journalArticlepeer-review


Airway epithelium is a regulator of innate immune responses to a variety of insults including cigarette smoke. Cigarette smoke alters the expression and the activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an alarmin, increases innate immunity Th2 responses. The aims of this study were to explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter both intracellular expression (mRNA and protein) and release of IL-33 in bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also explored.Mini-BALs, but not sera, from smokers show reduced concentrations of IL-33. The expression of IL-33 was increased also in bronchial epithelium from smokers. 20% CSE reduced IL-33 release but increased the mRNA for IL-33 by real time PCR and the intracellular expression of IL-33 in bronchial epithelial cells as confirmed by flow cytometry, immunocytochemistry and western blot analysis. The effect of CSE on IL-33 expression was also observed in primary bronchial epithelial cells. IL-33 expression was mainly concentrated within the cytoplasm of the cells. LPS, an agonist of TLR4, reduced IL-33 expression, and an inhibitor of TLR4 increased the intracellular expression of IL-33. In conclusion, the release of IL-33 is tightly controlled and, in smokers, an altered activation of TLR4 may lead to an increased intracellular expression of IL-33 with a limited IL-33 release.

Original languageEnglish
Pages (from-to)1630-1637
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number9
Publication statusPublished - 2014


  • Bronchial epithelial cell
  • Cigarette smoke
  • COPD
  • IL-33
  • Inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine


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