(NPF) IL-1 TNF. COX-2 mrna

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Stuart Robertson
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2 IL-6 酶 (COX-2)IL-6 (NPF) IL-1TNF NPF COX-2 IL-6 NPF 34 IL-6 COX-2 mrna NPF IL-6 COX-2 mrna COX-2 IL-6 mrna IL-6 COX-2 mrna IL-6 mrna COX-2 mrna NPF IL-6 COX-2 IL-6 mrna 酶 Abstract Nasal polyp (NP) is the most common mass lesion in nose. Although the pathogenesis remains unclear, NP has been regarded, at least by some authors, to be of inflammatory origin. During inflammation,, a complex series of reactions including vascular proliferation or dilatation, active extracellular matrix (ECM) remodeling and activation of immune mechanism will be elicited to promoter wound healing. Elevated levels of prostaglandins (PGs) and interleukin (IL)-5 are connected with the development of these phenomena. Inducible cyclooxygenase (COX-2) and 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-1 or tumor necrosis factor (TNF) alone or in combination with prostaglandin E (PG E) on IL-6 and COX-2 message RNA (mrna) synthesis in NPFs were investigated. 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. 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.

3 Meloxicam ( a specific COX-2 inhibitor) suppressed the induction of cytokines on IL-6 mrna levels, and these effects could be reversed by exogenous PG E. In situ hybridization revealed that IL-6 and COX-2 mrnas were detected primarily in fibroblasts, macrophages, and plasma cells. Aggregation of plasma cells ass well ass collagen deposition in vicinity to IL-6 mrna-producing fibroblasts was found. Rich vascularity around COX-2 mrna-positive fibroblasts was also identified. 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. COX-2 also contributes to NP development by promoting vasodilation and modulating the cytokine-induced IL-6 gene expression in NPFs. Keywords fibroblast, nasal polyp, cyclooxygenase, cytokine, prostaglandin. IL-6 COX-2 IL-6 (arachidonic acid) (COX-2) COX-1 COX-2 IL-6COX-2 IL-6COX-2 1. IL-6 COX-2 mrna 2. IL-1 TNF NPF IL-6 COX-2 mrna 3. COX-2 NPF IL-6 COX-2 mrna 4. IL-6 mrna NPF COX-2 mrna NPF

4 IL-6 B T IL-6 Th2 IL-6 (systemic scleosis) (cystic fibrosis) IL-6 IL-1TNF IL-6COX-2 IL-6 COX-2 mrna COX-2 NPF IL-6 COX-2 RNA 1. Lee CH, Rhee CS, Min YG. Cytokine gene expression in nasal polyps. Ann Otol Rhinol Laryngol. 1998; Unemori EN, Ehsani N, Wang M, Lee S, McGuire J, Amento EP. Interleukin-1 and transforming growth factor-alpha synergistic stimulation of metalloproteinases, PGE, and proliferation in human fibroblasts. Exp Cell Res. 1994; van Deuren M, Dofferhoff AS, van der Meer JW. Cytokines and the response to infection. J Pathol. 1992; Fries KM, Felch ME, Phipps RP. Interleukin-6 is an autocrine growth factor for murine lung fibroblast subsets. Am J Respir Cell Mol Biol.

5 1994; Bedard M, McClure CD, schiller NL, Francoeur C, Cantin A, Denis M. Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells implications for cystic fibrosis. Am J Respir Cell Mol Biol. 1993; Seibert K, Zhang Y, Leahy K, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase2 in inflammation and pain. Proc Natl Acad Sci USA. 1994; Houssiau FA, Devogelaer JP, Van Damme J, de Deuxchaisnes CN, Van Snick J. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum. 1988; Anderson GD, Hauser SD, McGarity KL, Bremer ME, Isakson PC, Gregory SA. Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin-6 in rat adjuvant arthritis. J Clin Invest. 1996; Picado C, Fernandez-Morata JC, Juan M, et al. Cyclooxygenase-2 mrna is down-expressed in nasal polyps from aspirin-sensitive asthmatics. Am J Respir Crit Care Med. 1999; Bruzzese N, Sica G, Iacopino F, et al. Growth inhibition of fibroblasts from nasal polyps and normal skin by lysine acetylsalicylate. Allergy. 1998;

VPM 152. INFLAMMATION: Chemical Mediators

VPM 152. INFLAMMATION: Chemical Mediators General Pathology VPM 152 INFLAMMATION: Chemical Mediators CHEMICAL MEDIATORS OF INFLAMMATION Definition: any messenger that acts on blood vessels, inflammatory cells or other cells to contribute to an