The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury

Author:

Chen Jingrui12,Zhou Xinjun3,Dai Nan3,Liu Xiaoyu3,Liu Shihan3,Zhang Haipeng34,Kong Lingcong12,Ma Hongxia1234

Affiliation:

1. College of Veterinary Medicine, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China

2. The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China

3. College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China

4. The Engineering Research Center of Bioreactor and Drug Development, Ministry of Education, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China

Abstract

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.

Funder

National Natural Science Foundation Regional Innovation and Development Joint Fund of China

National Natural Science Foundation of China

Jilin Provincial Department of Science and Technology-Major Science and Technology Project

Jilin Province Science and Technology Development Plan Project

Jilin Provincial Department of Science and Technology–Chinese Academy of Engineering Consulting Key Project

Publisher

MDPI AG

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3