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Toll interacting protein protects bronchial epithelial cells from bleomycin‐induced apoptosis
Author(s) -
Li Xiaoyun,
Kim Sharon E.,
Chen TingYun,
Wang Juan,
Yang Xia,
Tabib Tracy,
Tan Jiangning,
Guo Brandon,
Fung Sonia,
Zhao Jing,
Sembrat John,
Rojas Mauricio,
Shiva Sruti,
Lafyatis Robert,
St. Croix Claudette,
Alder Jonathan K.,
Di Y. Peter,
Kass Daniel J.,
Zhang Yingze
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902636rr
Subject(s) - bleomycin , apoptosis , toll , toll like receptor , microbiology and biotechnology , chemistry , immunology , cancer research , medicine , biology , immune system , innate immune system , genetics , biochemistry , chemotherapy
Idiopathic pulmonary fibrosis (IPF) is characterized by altered epithelial cell phenotypes, which are associated with myofibroblast accumulation in the lung. Atypical alveolar epithelial cells in IPF express molecular markers of airway epithelium. Polymorphisms within and around Toll interacting protein (TOLLIP) are associated with the susceptibility to IPF and mortality. However, the functional role of TOLLIP in IPF is unknown. Using lung tissues from IPF and control subjects, we showed that expression of TOLLIP gene in the lung parenchyma is globally lower in IPF compared to controls. Lung cells expressing significant levels of TOLLIP include macrophages, alveolar type II, and basal cells. TOLLIP protein expression is lower in the parenchyma of IPF lungs but is expressed in the atypical epithelial cells of the distal fibrotic regions. Using overexpression and silencing approaches, we demonstrate that TOLLIP protects cells from bleomycin‐induced apoptosis using primary bronchial epithelial cells and BEAS‐2B cells. The protective effects are mediated by reducing mitochondrial reactive oxygen species (ROS) levels and upregulating autophagy. Therefore, global downregulation of the TOLLIP gene in IPF lungs may predispose injured lung epithelial cells to apoptosis and to the development of IPF.