TY - JOUR
T1 - Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis
AU - Tominaga, Masaki
AU - Okamoto, Masaki
AU - Kawayama, Tomotaka
AU - Matsuoka, Masanobu
AU - Kaieda, Shinjiro
AU - Sakazaki, Yuki
AU - Kinoshita, Takashi
AU - Mori, Daisuke
AU - Inoue, Akira
AU - Hoshino, Tomoaki
N1 - Funding Information:
This work was supported by JSPS KAKENHI grants (Grant numbers 25461202 and 16K09595 ) (T.H.), grants from the Japan Foundation for Aging and Health , Ishibashi's Fund for the Promotion of Science , and a JSPS KAKENHI grant (Grant number 25860663 ) (M.O.), grants from the Kaibara Morikazu Medical Promotion Science Foundation , the Ishibashi Foundation for the Promotion of Science, and a Grant-in-Aid for Young Scientists from the Ministry of Education, Culture, Sports, Science and Technology (Grant number 26860619 ) (T.K.), and by a grant from the Takeda Science Foundation (S.K.).
Publisher Copyright:
© 2017 The Japanese Respiratory Society
PY - 2017/9
Y1 - 2017/9
N2 - Background Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. Methods To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. Results IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. Conclusions IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF.
AB - Background Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. Methods To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. Results IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. Conclusions IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF.
KW - Anticancer drug
KW - IL-38
KW - Interstitial lung disease
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U2 - 10.1016/j.resinv.2017.06.001
DO - 10.1016/j.resinv.2017.06.001
M3 - Article
C2 - 28942884
AN - SCOPUS:85028338498
VL - 55
SP - 293
EP - 299
JO - Respiratory Investigation
JF - Respiratory Investigation
SN - 2212-5345
IS - 5
ER -