Published ahead of print on August 14, 2003, doi:10.1165/rcmb.2003-0071OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2003-0071OC Characterization of Interleukin-4–Stimulated Nasal Polyp FibroblastsDepartments of Medicine, Pharmacology, and Otolaryngology, Asthma and Allergic Disease Center, Beirne Carter Center for Immunology Research, University of Virginia Health System, Charlottesville, Virginia Address correspondence to: John W. Steinke, Ph.D., Asthma and Allergic Disease Center, Box 801355, University of Virginia Health System, Charlottesville, VA 22908. Email: js3ch{at}virginia.edu 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-ß1 and -ß2) 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.
Abbreviations: chronic hyperplastic eosinophilic sinusitis, CHES • cyclooxygenase, COX • cysteinyl leukotriene, CysLT • enzyme-linked immunosorbent assay, ELISA • fetal bovine serum, FBS • 5-lipoxygenase activating protein, FLAP • glyceraldehyde-3-phosphate dehydrogenase, GAPDH • granulocyte macrophage–colony-stimulating factor, GM-CSF • interferon, IFN • interleukin, IL • 5-lipoxygenase, 5-LO • latency-associated protein, LAP • lysophosphatidic acid, LPA • leukotriene, LT • nasal polyposis, NP • ostiomeatal complex, OMC • phosphate-buffered saline, PBS • phospholipase A2, PLA2 • ribonuclease protection assay, RPA • reverse transcriptase–polymerase chain reaction, RT-PCR • transforming growth factor, TGF • tumor necrosis factor, TNF • vascular cell adhesion molecule, VCAM This article has been cited by other articles:
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