title: Inducible cyclooxygenase and interleukin 6 gene expressions in nasal polyp fibroblasts: possible implication in the pathogenesis of nasal polyposis.
abstract: BACKGROUND
  Inflammation is believed to be related to the pathogenesis of nasal polyp (NP). Inducible cyclooxygenase (COX-2) and interleukin (IL) 6 are important mediators of inflammation. However, no information is available regarding the expression of these mediators in nasal polyp fibroblasts (NPFs). The inductive effects of proinflammatory cytokines (IL-1alpha or tumor necrosis factor alpha) alone or in combination with prostaglandin E(2) on IL-6 and COX-2 messenger RNA (mRNA) synthesis in NPFs were investigated.
  
  
  METHODS
  The expressions of IL-6 and COX-2 mRNAs in NPFs and in 34 surgical specimens of NP were detected by Northern blot and in situ hybridization.
  
  
  RESULTS
  Significant amounts of constitutive IL-6 and COX-2 mRNAs were produced in NPFs. Cytokines induced IL-6 and COX-2 mRNA synthesis in NPFs. Meloxicam (a specific COX-2 inhibitor) suppressed the induction of cytokines on IL-6 mRNA levels, and these effects could be reversed by exogenous prostaglandin E(2). In situ hybridization revealed that IL-6 and COX-2 mRNAs were detected primarily in fibroblasts, macrophages, and plasma cells. Aggregation of plasma cells as well as collagen deposition in vicinity to IL-6 mRNA-producing fibroblasts was found. Rich vascularity around COX-2 mRNA(+) fibroblasts was also identified.
  
  
  CONCLUSIONS
  The pathogenesis of nasal polyposis involves NPFs through synthesizing IL-6 to modulate the activation of immune responses (plasma cell formation) and synthesis of stroma. Inducible cyclooxygenase also contributes to NP development by promoting vasodilatation and modulating the cytokine-induced IL-6 gene expression in NPFs.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Liu
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hong
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Hsiao
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Wang
authors.forename: Juo-Song
authors.initials: JS
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Sze-Kwan
authors.initials: SK
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics*; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics*; D008565:Membrane Proteins; D009298:Nasal Polyps / Q000235:genetics* / Q000473:pathology*; D010120:Oxytocics / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D010120:Oxytocics; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone