Synergistic Induction of Macrophage Inflammatory Protein-3α/CCL20 Production by Interleukin-17A and Tumor Necrosis Factor-αin Nasal Polyp Fibroblasts

Abstract

Background: Accumulation of T cells and immature dendritic cells (DCs) is one of the characteristic features of nasal polyps. However, the question remains why these cells accumulate in nasal polyp tissue. Macrophage inflammatory protein-3α (MIP-3α/CCL20) is a chemokine involved in the migration of T cells and immature DCs into inflammatory tissue sites. Fibroblasts are a rich source of cytokines and chemokines. The objective of this study was to demonstrate the expression of MIP-3α/CCL20 in nasal polyp fibroblasts after stimulation with proinflammatory cytokines such as interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α).Methods: Fibroblast lines were established from nasal polyps. MIP-3α/CCL20 mRNA expression was evaluated by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). The amount of MIP-3α/CCL20 in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA).Results: IL-17A and TNF-α synergistically induced MIP-3α/CCL20 production by nasal polyp fibroblasts in a dose- and time-dependent manner. This synergy was observed by stimulation with TNF-α plus IL-17A or IL-17F, but not IL-17E.Conclusions: Nasal polyp fibroblasts, by producing MIP-3α/CCL20, may play an important role in the recruitment of T cells and DCs in upper airway inflammatory lesions such as nasal polyps. Keywords: CCR6 ligand, chronic sinusitis, MIP-3α/CCL20, IL-17 family members