Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis
Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis
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DOI：
10.1016/j.resinv.2017.06.001
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发表时间：
2017-09-01
影响因子：
3.1
通讯作者：
Hoshino, Tomoaki
中科院分区：
文献类型：
--
作者：
Tominaga, Masaki;Okamoto, Masaki;Hoshino, Tomoaki
背景资料：白细胞介素（IL）-38是IL-1家族的成员，与IL-1受体拮抗剂（IL-1 Ra）和IL-36受体拮抗剂（IL-36 Ra）具有高度同源性。方法：采用实时荧光定量PCR技术，对不同组织中IL-38 mRNA的表达进行分析，以确定IL-38 mRNA的表达模式。在12例特发性肺纤维化/普通型间质性肺炎（IPF/UIP）、5例IPF急性加重和10例抗癌药物诱导的ILD（5例博莱霉素和5例表皮生长因子受体酪氨酸激酶抑制剂）患者的肺组织样本中，半定量评价了抗人IL-38单克隆抗体（克隆H127 C）的免疫组织化学反应性。结果：IL-38在肺、脾、滑膜细胞和外周血单个核细胞中呈强阳性表达，在胰腺和肌肉中表达较低。22只正常肺组织中IL-38蛋白均不强表达。相比之下，4/5例（80%）IPF急性加重患者和100%（10/10）药物诱导ILD患者的肺中IL-38过表达。IL-38过表达仅限于增生的II型肺细胞，这被认为反映了ILD弥漫性肺泡损伤后的再生变化。结论：IL-38可能在抗癌药物诱导的肺损伤和IPF急性加重的急性和/或慢性炎症中发挥重要作用。(C)2017日本呼吸学会Elsevier B. V.出版，保留所有权利。
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. (C) 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.