Characterization of interleukin-4-stimulated nasal polyp fibroblasts.
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.
Steinke
John W
JW
Department of Medicine, , University of Virginia Health System, Charlottesville, VA 22908, USA. js3ch@virginia.edu
Crouse
Charles D
CD
Bradley
Dewayne
D
Hise
Kathleen
K
Lynch
Kevin
K
Kountakis
Stilianos E
SE
Borish
Larry
L
D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000502:physiology*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009298:Nasal Polyps / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000235:genetics / Q000378:metabolism; D012852:Sinusitis / Q000276:immunology / Q000473:pathology
D018925:Chemokines; D016207:Cytokines; D018793:Interleukin-13; D015289:Leukotrienes; D008565:Membrane Proteins; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D018077:Receptors, Leukotriene; D015847:Interleukin-4; C083169:leukotriene D4 receptor