Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Gene Expressions and Their Differential Regulation by Proinflammatory Cytokines and Prostaglandin in Nasal Polyp Fibroblasts

Abstract

Chronic inflammation of the paranasal sinus leads to nasal polyp (NP) formation. In this study, we investigated the effect of stimulation of the proinflammatory cytokines interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) and prostaglandin (PG) E₂ on the production of messenger RNA (mRNA) of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in nasal polyp fibroblasts (NPFs) and nasal mucosa fibroblasts (NFs). The mRNAs of IL-1α, TNF-α, MMP-1, and TIMP-1 in 40 surgical specimens of NPs were studied by in situ hybridization to corroborate the in vitro findings. The results indicated a significant amount of constitutive MMP-1 mRNA in NPFs and cytokine-induced MMP-1 steady-state mRNAs in NFs. The effect of stimulation of cytokines on TIMP-1 mRNA synthesis was unremarkable in NPFs and NFs. Exogenous PGE₂ enhanced cytokine-stimulated MMP-1 mRNA synthesis in NPFs. In situ hybridization revealed that cells expressing MMP-1 and TIMP-1 mRNAs (primarily plasma cells, fibroblasts, and endothelial cells) gathered around areas with loose stroma, suggestive of rapid extracellular matrix degradation. These data suggest that the pathogenesis of nasal polyposis could be related to production of MMP-1 and consequent promotion of matrix collagenolysis.

Keywords

interleukin-1α matrix metalloproteinase-1 nasal polyp prostaglandin tissue inhibitor of metalloproteinase-1 tumor necrosis factor-α

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