Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma

Christelle Doucet, Danièle Brouty-Boyé, Corine Pottin-Clémenceau, Giorgio Walter Canonica, Claude Jasmin, Bruno Azzarone

Research output: Contribution to journalArticlepeer-review

Abstract

Airway hyperresponsiveness leading to subepithelial fibrosis is mediated by inflammatory cells activated by T helper (Th) 2-derived cytokines such as IL-4 and IL-5. By analyzing the phenotype and response of human lung fibroblasts derived from either fetal (ICIG7) or adult (CCL202) tissue as well as from a Th2-type stromal reaction (FPA) to IL-4 and IL-13, we provide evidence that human lung fibroblasts may behave as inflammatory cells upon activation by IL-4 and IL-13. We show that the three types of fibroblasts constitute different populations that display a distinct pattern in cell surface molecule expression and proinflammatory cytokine and chemokine release. All fibroblasts express functional but different IL-4/IL-13 receptors. Thus, while IL-4 receptor (R) α and IL-13Rα1 chains are present in all the cells, CCL202 and FPA fibroblasts coexpress the IL13Rα2 and the IL-2Rγ chain, respectively, suggesting the existence of a heterotrimeric receptor (IL-4Rα/IL-13Rα/IL2Rγ) able to bind IL-4 and IL-13. Stimulation with IL-4 or IL-13 triggers in the fibroblasts a differential signal transduction and upregulation in the expression of β1 integrin and vascular cell adhesion molecule 1 and in the production of IL-6 and monocyte chemoattractant protein 1, two inflammatory cytokines important in the pathogenesis of allergic inflammation. Our results suggest that when activated by IL-4 and IL-13, different subsets of lung fibroblasts may act as effector cells not only in the pathogenesis of asthma but also in lung remodeling processes. They may also differentially contribute to trigger and maintain the recruitment, homing, and activation of inflammatory cells.

Original languageEnglish
Pages (from-to)2129-2139
Number of pages11
JournalJournal of Clinical Investigation
Volume101
Issue number10
Publication statusPublished - May 15 1998

Keywords

  • Adhesion molecules
  • Airway inflammation
  • Human lung fibroblasts
  • Proinflammatory cytokines
  • Signal transduction

ASJC Scopus subject areas

  • Medicine(all)

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