RT Journal Article
SR Electronic
T1 In vivo effects of corticosteroid plus long-acting beta2-agonist on the expression of B7-H1/PD-L1 in double-stranded RNA-induced lung inflammation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P863
VO 44
IS Suppl 58
A1 Saaka Hamano
A1 Koichiro Matsumoto
A1 Satoru Fukuyama
A1 Keiko Kan-o
A1 Nanae Seki
A1 Ken Tonai
A1 Takako Nakano
A1 Hiromasa Inoue
A1 Yoichi Nakanishi
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P863.abstract
AB Background and Aim: Airway viral infection exacerbates asthma and COPD. B7-H1/PD-L1 is a coinhibitory molecule implicated in an escape mechanism of viruses from the host immune systems. This escape may induce viral persistence and lead to the exacerbation. In ERS international congress 2013, we showed that an analog of viral double-strand RNA, polyinosinic-polycytidylic acid (poly I:C), upregulated the expression of B7-H1/PD-L1 on airway epithelial cells in vitro, which was resistant to corticosteroid treatment. Although this resistance was overcome by addition of long-acting beta2-agonist (LABA), in vivo evidence remained uncertain. We examined the effect of corticosteroid plus LABA on the expression of B7-H1/PD-L1 in vivo.Methods: We established a murine model of double-stranded RNA-induced inflammation by an intratracheal administration (i.t.) of poly I:C. The expression of B7-H1/PD-L1 in epithelial cells was assessed by flow cytometry as well as assessment of inflammation in bronchoalveolar lavage fluid (BALF). The effects of ciclesonide and/or indacaterol (i.t.) were examined.Results: Poly I:C induced upregulation of B7-H1/PD-L1 in epithelial cells and neutrophilia in BALF. The upregulation was suppressed by low-concentration ciclesonide in combination with indacaterol. This combination also suppressed neutrophilia in BALF.Conclusion: Corticosteroid plus LABA attenuates double-stranded RNA-induced upregulation of B7-H1/PD-L1 in vivo. This mechanism may partly explain a beneficial effect of combination therapy on virus-associated exacerbation of asthma and COPD.