IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts

Séverine Létuvé, Stéphane Lajoie-Kadoch, Séverine Audusseau, Marc E. Rothenberg, Pierre Olivier Fiset, Mara S. Ludwig, Qutayba Hamid

Research output: Contribution to journalArticlepeer-review

Abstract

Background: IL-17E is a new TH2 cytokine that promotes airway eosinophilia in mice. IL-17E proinflammatory activity has been proposed to involve induction of cytokine and chemokine production. Recruitment of inflammatory cells may be mediated by tissue-resident cells. Objective: This study aimed to evaluate whether fibroblasts represent a target of IL-17E for the production of eosinophil active mediators in the lung. Methods: Expression of IL-17B receptor (IL-17BR), a receptor for IL-17E, was evaluated by immunofluorescent staining, Western blot, and real-time PCR in human primary lung fibroblasts. Mediator production was analyzed by using real-time PCR and ELISA after stimulation of fibroblasts with IL-17E alone or in combination with TNF-α and TGF-β1. Expression of IL-17E and of eosinophil major basic protein was evaluated by immunohistochemistry in bronchial biopsies from subjects with asthma. Results: Human primary lung fibroblasts constitutively expressed IL-17BR. IL-17BR mRNA levels were increased in cells stimulated with TNF-α and decreased with TGF-β1. IL-17E slightly upregulated CC chemokine ligand (CCL)-5, CCL-11, GM-CSF, and CXC chemokine ligand (CXCL)-8 mRNA in fibroblasts. Moreover, IL-17E and TNF-α synergistically induced GM-CSF and CXCL-8 mRNA. IL-17E also potentiated the upregulation of CXCL-8 transcripts observed with TGF-β1. In contrast, TGF-β1 decreased IL-17E-induced CCL-11 mRNA. The capacity of IL-17E to enhance GM-CSF and CXCL-8 responses to TNF-α was accompanied by production and secretion of both proteins by lung fibroblasts. Finally, IL-17E was detected in asthma in eosinophil-infiltrated bronchial submucosa. Conclusion: IL-17E may contribute to the induction and maintenance of eosinophilic inflammation in the airways by acting on lung fibroblasts. This study supports a role for IL-17E in asthma pathophysiology.

Original languageEnglish (US)
Pages (from-to)590-596
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume117
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Allergic inflammation
  • Asthma
  • Chemokines
  • Cytokine receptors
  • Cytokines
  • IL-17E
  • Lung fibroblasts
  • TGF-β
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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