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A1314 - Soluble ST2 (sST2)/ IL-33 Balance Regulates Neutrophil Chemotaxis Release from Bronchial Epithelial Cells
Author Block: M. Watanabe1, M. Sada2, K. Nakamoto2, T. Inui2, Y. Ogawa1, T. Yokoyama1, K. Honda1, T. Saraya3, D. Kurai2, H. Ishii4, H. Takizawa5; 1Department of Respiratory Medicine, Kyorin University, Tokyo, Japan, 2Kyorin University, Tokyo, Japan, 3Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Japan, 4Respiratory Medicine, Kyorin University Hospital, Tokyo, Japan, 5Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Rationale: Interleukin (IL)-33 involves in neutrophilic airway inflammation in viral infection. Soluble ST2 (sST2), a decoy receptor for interleukin IL-33, is released from bronchial epithelial cells. These suggest that sST2/IL-33 balance regulates airway neutrophilic inflammation and affects to asthma phenotype. Aim: To clarify the mechanism that regulates sST2/IL-33 balance and its effect on chemotaxis production in bronchial epithelial cells. Method: We stimulated normal human bronchial epithelial cells (NHBE) with IL-33 and measured IL-8 and CXCL1 levels in culture supernatant using ELISA. We next stimulated NHBE with phorbol 12-myristate 13-acetate (PMA), and obtained culture supernatant and cell lysate. We also stimulated NHBE with proinflammatory cytokines (TNFα and IL-1β) and toll-like receptor ligands (i.e. TLR-1/2, -2, -3, -4, and -5: Pam3CSK4, lipoteichoic acid (LTA), poly(I:C), lipopolysaccharide (LPS), and flagellin, respectively). We quantified sST2 levels in culture supernatant using ELISA and examined expression of cell-surface ST2 (ST2L) and intracellular sST2 using western blot. Results: IL-33 enhanced IL-8 and CXCL1 release from NHBE with dose-dependent manner. PMA stimulated sST2 release, increased intracellular sST2 expression, and decreased cell-surface ST2L expression in NHBE. Pam3CSK4, LTA, and flagellin enhanced sST2 release from NHBE, whereas poly(I:C), LPS, TNFα and IL-1β did not. Discussion: Previous report demonstrated that IL-33 is released from bronchial epithelial cells by viral infection, necrosis, and allergen exposure; sST2 is released from inflamed bronchial cells. Our data showed that IL-33 stimulates neutrophil-chemotaxis release from bronchial epithelial cells. We also showed that infectious and inflammatory stimuli increased sST2 production and reciprocally decreased cell-surface ST2L expression on bronchial epithelial cells. These indicate that viral/bacterial infection, inflammatory/necrotic stimuli, and allergen-exposure disrupt the balance of sST2/ST2L/IL-33, which influence neutrophil-chemotaxis production in bronchus and potentially affect to asthma phenotype. Conclusions: Infection and inflammation modulate sST2/ST2L/IL-33 balance that regulates neutrophil-chemotaxis release in bronchial epithelial cells.