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Article

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

by
Jingrui Chen
1,2,
Xinjun Zhou
3,
Nan Dai
3,
Xiaoyu Liu
3,
Shihan Liu
3,
Haipeng Zhang
3,4,
Lingcong Kong
1,2,* and
Hongxia Ma
1,2,3,4,*
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
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(8), 4567; https://doi.org/10.3390/ijms25084567
Submission received: 29 March 2024 / Revised: 15 April 2024 / Accepted: 19 April 2024 / Published: 22 April 2024
(This article belongs to the Section Molecular Pharmacology)
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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.
Keywords: mPEG-SPA-MDSPI16; pharmaceutical properties; ALI; anti-inflammatory activity; anti-inflammatory mechanism mPEG-SPA-MDSPI16; pharmaceutical properties; ALI; anti-inflammatory activity; anti-inflammatory mechanism

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MDPI and ACS Style

Chen, J.; Zhou, X.; Dai, N.; Liu, X.; Liu, S.; Zhang, H.; Kong, L.; Ma, H. The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury. Int. J. Mol. Sci. 2024, 25, 4567. https://doi.org/10.3390/ijms25084567

AMA Style

Chen J, Zhou X, Dai N, Liu X, Liu S, Zhang H, Kong L, Ma H. The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury. International Journal of Molecular Sciences. 2024; 25(8):4567. https://doi.org/10.3390/ijms25084567

Chicago/Turabian Style

Chen, Jingrui, Xinjun Zhou, Nan Dai, Xiaoyu Liu, Shihan Liu, Haipeng Zhang, Lingcong Kong, and Hongxia Ma. 2024. "The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury" International Journal of Molecular Sciences 25, no. 8: 4567. https://doi.org/10.3390/ijms25084567

APA Style

Chen, J., Zhou, X., Dai, N., Liu, X., Liu, S., Zhang, H., Kong, L., & Ma, H. (2024). The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury. International Journal of Molecular Sciences, 25(8), 4567. https://doi.org/10.3390/ijms25084567

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