The cross-talk between innate immunity and acquired immunity in exacerbation of airway inflammation in asthmatic attack

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: FUJISAWA TOMOYUKI 浜松医科大学, 医学部, 助教 (20402357)
• Research Collaborator: MORI KAZUTAKA 浜松医科大学, 医学部, 大学院生 ; YAMANAKA KATSUMASA 浜松医科大学, 医学部, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 気管支喘息 / 気道炎症 / IL-17A / Toll like receptor / 炎症性サイトカイン / 自然免疫 / 獲得免疫

Outline of Final Research Achievements

The interaction between IL-17A and TLR3 activation in airway epithelium remains poorly understood. In this study, we demonstrated that IL-17A and polyI:C, the ligand of TLR3, synergistically induced proinflammatory cytokine and chemokine (G-CSF, IL-8) mRNA and protein expression. Inhibition of the NF-κB pathway using NF-κB p65 siRNA, or BAY11-7082 (IκB-α inhibitor) attenuated the IL-17A/polyI:C-induced synergistic expression of proinflammatory cytokines. Knockdown of IRF3 using siRNA also decreased the synergistic gene expression. In western blotting analysis, co-treatment with IL-17A and polyI:C augmented IκB-α phosphorylation compared to polyI:C treatment alone. These findings demonstrate that IL-17A and TLR3 activation act in concert to potentiate proinflammatory responses in the airway epithelium via NF-κB/IRF3 activation, and that enhanced activation of the NF-κB pathway play a key role in the synergism.

Free Research Field

呼吸器内科学