Characterization of Interleukin-4-Stimulated Nasal Polyp Fibroblasts

John W. Steinke, Charles D. Crouse, Dewayne Bradley, Kathleen Hise, Kevin Lynch, Stilianos E Kountakis, Larry Borish

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Chronic hyperplastic eosinophilic sinusitis is an inflammatory disease that results in the accumulation of eosinophils, fibroblasts, mast cells, and goblet cells at the site of injury. A common feature of this disease is the presence of nasal polyposis (NP). The current studies were designed to assess the contribution of interleukin (IL)-4 to fibroblast-mediated inflammation in chronic hyperplastic eosinophilic sinusitis/NP. In addition, we hypothesized that cysteinyl leukotrienes (CysLT) may directly influence fibroblast-mediated fibrotic and remodeling pathways in this disorder. Fibroblasts were isolated from NP tissue. All fibroblast lines expressed the IL-4 receptor. IL-4 induced changes in mRNA and protein expression of fibrotic (transforming growth factor-β1 and -β2) and inflammatory cytokines and chemokines (IL-6 and CCL11) by fibroblasts as measured by semiquantitative and quantitative polymerase chain reaction, RNase protection assay, and enzyme-linked immunosorbent assay. The expression of CysLT and other proinflammatory lipid receptors on fibroblasts was evaluated. CysLT1 and CysLT2 receptors were not expressed on fibroblasts; however, LPA1 receptor was constitutively expressed and LPA2 receptor expression was upregulated by IL-4. The metabolic cascade involved in CysLT synthesis was not expressed in fibroblasts and could not be induced by IL-4 treatment.

Original languageEnglish (US)
Pages (from-to)212-219
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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