Oncotarget

Research Papers:

Triptolide mitigates radiation-induced pneumonitis via inhibition of alveolar macrophages and related inflammatory molecules

Chun Chen, Shanmin Yang, Mei Zhang, Zhenhuan Zhang, Steven B. Zhang, Bing Wu, Jinsheng Hong, Weijian Zhang, Jianhua Lin, Paul Okunieff and Lurong Zhang _

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Oncotarget. 2017; 8:45133-45142. https://doi.org/10.18632/oncotarget.16456

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Abstract

Chun Chen1,*, Shanmin Yang2,*, Mei Zhang2, Zhenhuan Zhang2, Steven B. Zhang2, Bing Wu3, Jinsheng Hong3, Weijian Zhang3, Jianhua Lin3, Paul Okunieff2 and Lurong Zhang2,3

1Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China

2Department of Radiation Oncology, University of Florida, Gainesville 32610, Florida, USA

3Fujian Platform for Medical Research at First Affiliated Hospital, Fujian Key Lab of Individualized Active Immunotherapy and Key Laboratory of Radiation Biology of Fujian Province Universities, Fuzhou 350005, China

*These authors contributed equally to this work

Correspondence to:

Chun Chen, email: chenchun-0428@163.com

Lurong Zhang, email: lz8506@163.com

Keywords: Triptolide, radiotherapy, pneumonitis, alveolar macrophage, inflammative molecules

Received: January 09, 2017     Accepted: March 14, 2017     Published: March 22, 2017

ABSTRACT

Ionizing radiation-induced pulmonary injury is a major limitation of radiotherapy for thoracic tumors. We have demonstrated that triptolide (TPL) could alleviate IR-induced pneumonia and pulmonary fibrosis. In this study, we explored the underlying mechanism by which TPL mitigates the effects of radiotoxicity. The results showed that:

(1) Alveolar macrophages (AMs) were the primary inflammatory cells infiltrating irradiated lung tissues and were maintained at a high level for at least 17 days, which TPL could reduce by inhibiting of the production of macrophage inflammatory protein-2 (MIP-2) and its receptor CXCR2.

(2) Stimulated by the co-cultured irradiated lung epithelium, AMs produced a panel of inflammative molecules (IMs), such as cytokines (TNF-α, IL-6, IL-1α, IL-1β) and chemokines (MIP-2, MCP-1, LIX). TPL-treated AMs could reduce the production of these IMs. Meanwhile, AMs isolated from irradiated lung tissue secreted significantly high levels of IMs, which could be dramatically reduced by TPL.

(3) TPL suppressed the phagocytosis of AMs as well as ROS production.

Our results indicate that TPL mitigates radiation-induced pulmonary inflammation through the inhibition of the infiltration, IM secretion, and phagocytosis of AMs.


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