RT Journal Article
SR Electronic
T1 Targeting IL-17 attenuates hypoxia-induced pulmonary hypertension through downregulation of β-catenin
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 564
OP 578
DO 10.1136/thoraxjnl-2018-211846
VO 74
IS 6
A1 Wang, Lei
A1 Liu, Jie
A1 Wang, Wang
A1 Qi, Xianmei
A1 Wang, Ying
A1 Tian, Bo
A1 Dai, Huaping
A1 Wang, Jing
A1 Ning, Wen
A1 Yang, Ting
A1 Wang, Chen
YR 2019
UL http://thorax.bmj.com/content/74/6/564.abstract
AB Background The role of interleukin 17 (IL-17) in hypoxic pulmonary hypertension (HPH) remains unclear. This study is designed to explore whether IL-17 is a potential target for HPH treatment.Methods Clinic samples from the lung tissue and serum were obtained from qualified patients. Western blotting, immunohistochemistry and/or ELISA were used to measure the expression of relevant proteins. HPH models were established in C57BL/6 wild-type (WT) and IL-17 −/− mice and were treated with exogenous recombinant mouse IL-17 (rmIL-17) or an IL-17 neutralising antibody. Assays for cell proliferation, angiogenesis and adhesion were employed to analyse the behaviours of human pulmonary arterial endothelial cells (HPAECs). A non-contact Transwell coculture model was used to evaluate intercellular interactions.Results Expression of IL-17 was increased in lung tissue of both patients with bronchiectasis/COPD-associated PH and HPH mouse model. Compared with WT mice, IL-17 −/− mice had attenuated HPH, whereas administration of rmIL-17 aggravated HPH. In vitro, recombinant human IL-17 (rhIL-17) promoted proliferation, angiogenesis and adhesion in HPAECs through upregulation of Wnt3a/β-catenin/CyclinD1 pathway, and siRNA-mediated knockdown of β-catenin almost completely reversed this IL-17-mediated phenomena. IL-17 promoted the proliferation but not the migration of human pulmonary arterial smooth muscle cells (HPASMCs) cocultured with HPAECs under both normoxia and hypoxia, but IL-17 had no direct effect on proliferation and migration of HPASMCs. Blockade of IL-17 with a neutralising antibody attenuated HPH in WT mice.Conclusions IL-17 contributes to the pathogenesis of HPH through upregulation of β-catenin expression. Targeting IL-17 might provide potential benefits for alternative therapeutic strategies for HPH.