TY - JOUR T1 - Essential role of IRF-3 in COPD exacerbation mouse model JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA3638 VL - 48 IS - suppl 60 SP - PA3638 AU - Takashi Ishii AU - Keisuke Hosoki AU - Yuichi Nikura AU - Takahide Nagase AU - Naomi Yamashita Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA3638.abstract N2 - Rationale: The acute exacerbation of COPD is critical for the prognosis of the disease. Innate immunity may be involved in COPD exacerbation triggered by infection. However, its precise mechanism and pathogenesis associated with innate immune systems is unclear. Interferon regulatory factor-3 (IRF-3) as well as NF-kB is a transcriptional factor which is activated by the stimulation of TLR 4. In this study, we clarified the role of IRF-3 in COPD exacerbation.Methods: Intranasal administration of porcine pancreatic elastase (PPE), followed by LPS administration was carried out to C57BL/6 (WT) or IRF3KO male mice. Sequential quantitative change of emphysema was evaluated by micro-CT for six weeks. Bronchial alveolar lavage fluid (BALF) and lung tissue were collected and analyzed one day after the last LPS treatment. Functional analysis such as phagocytosis, apoptosis, and autophagic activity were performed using specific cell population derived from lungs and BALF by cell sorting.Results: IRF3KO mice showed suppressed enlargement of alveolar air-space in micro-CT imaging and histopathology. The mRNA expressions of MCP-1, MIP-1α, TNF-α,as well as IP-10, were decreased in the lung of IRF3KO mice. However, the number of neutrophils was increased in the BALF of IRF3KO mice. The functional analysis revealed that phagocytosis, apoptosis and autophagic activity of neutrophils from the lung of IRF3KO mouse was suppressed, compared with WT mice.Conclusion: IRF-3 promotes a further emphysema formation induced with LPS preceded by PPE, based on distinct profiles of cytokines and chemokines involved in COPD pathogenesis. Functional regulation of neutrophils by IRF-3 pathway contributed to the pathogenesis of COPD exacerbation. ER -