Characterization of interleukin-4-stimulated nasal polyp fibroblasts

Am J Respir Cell Mol Biol. 2004 Feb;30(2):212-9. doi: 10.1165/rcmb.2003-0071OC. Epub 2003 Aug 14.

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-beta1 and -beta2) 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, LPA(1) receptor was constitutively expressed and LPA(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Fibroblasts / immunology
  • Fibroblasts / physiology*
  • Humans
  • Interleukin-13 / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism*
  • Leukotrienes / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nasal Polyps / immunology
  • Nasal Polyps / pathology*
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-4 / genetics
  • Receptors, Interleukin-4 / metabolism
  • Receptors, Leukotriene / genetics
  • Receptors, Leukotriene / metabolism
  • Sinusitis / immunology
  • Sinusitis / pathology

Substances

  • Chemokines
  • Cytokines
  • Interleukin-13
  • Leukotrienes
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Interleukin-4
  • Receptors, Leukotriene
  • Interleukin-4
  • leukotriene D4 receptor