Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis

Masaki Tominaga, Masaki Okamoto, Tomotaka Kawayama, Masanobu Matsuoka, Shinjiro Kaieda, Yuki Sakazaki, Takashi Kinoshita, Daisuke Mori, Akira Inoue, Tomoaki Hoshino

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)293-299
Number of pages7
JournalRespiratory Investigation
Volume55
Issue number5
DOIs
Publication statusPublished - 2017 Sep

Keywords

  • Anticancer drug
  • IL-38
  • Interstitial lung disease

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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