| Autor: |
Chen J; College of Veterinary Medicine, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China.; The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China., Zhou X; College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China., Dai N; College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China., Liu X; College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China., Liu S; College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China., Zhang H; College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China.; The Engineering Research Center of Bioreactor and Drug Development, Ministry of Education, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China., Kong L; College of Veterinary Medicine, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China.; The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China., Ma H; College of Veterinary Medicine, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China.; The Key Laboratory of New Veterinary Drug Research and Development of Jilin Province, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China.; College of Life Science, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China.; The Engineering Research Center of Bioreactor and Drug Development, Ministry of Education, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, China. |
| Abstrakt: |
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 IC 50 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. |
