Inducible cyclooxygenase and interleukin 6 gene expressions in nasal polyp fibroblasts: possible implication in the pathogenesis of nasal polyposis.

Abstract

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. 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. 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. 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.