Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea
Tumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicin...
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doaj-c5371672d24640778cd702dceb3aea1b2020-11-24T21:12:52ZengMDPI AGInternational Journal of Molecular Sciences1422-00672016-11-011711194010.3390/ijms17111940ijms17111940Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China SeaNingyuan Wang0Yan Huang1An Li2Hailong Jiang3Jie Wang4Jianzhong Li5Lei Qiu6Ka Li7Yiming Lu8School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, ChinaDepartment of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, ChinaDepartment of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, ChinaDepartment of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, ChinaDepartment of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, ChinaDepartment of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, ChinaDepartment of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, ChinaBiomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, ChinaTumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has been used in the treatment of inflammatory diseases in China for centuries. In this research, we constructed a venom gland T7 phage display library of the sea snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF-α and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H-TL1). In enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analyses, H-TL1 inhibited the interaction between TNF-α and TNF receptor 1 (TNFR1). Further, H-TL1 attenuated the cytotoxicity of TNF-α in L929 cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. H-TL1 also decreased the mRNA expression of TNF-α/TNFR1 downstream targets and suppressed the phosphorylation of well-characterized proteins of downstream signal transduction pathways in HEK-293 cells. In vivo data demonstrated that H-TL1 protects animals against dextran sodium sulfate (DSS)-induced acute colitis and lipopolysaccharide (LPS)-induced acute shock. Given its significant anti-inflammatory activity in vitro and in vivo, H-TL1 is a potential peptide for the development of new agents to treat TNF-α-associated inflammatory diseases.http://www.mdpi.com/1422-0067/17/11/1940H-TL1Hydrophis cyanocinctusanti-inflammatoryinflammatory bowel diseasesTNF-α |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ningyuan Wang Yan Huang An Li Hailong Jiang Jie Wang Jianzhong Li Lei Qiu Ka Li Yiming Lu |
spellingShingle |
Ningyuan Wang Yan Huang An Li Hailong Jiang Jie Wang Jianzhong Li Lei Qiu Ka Li Yiming Lu Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea International Journal of Molecular Sciences H-TL1 Hydrophis cyanocinctus anti-inflammatory inflammatory bowel diseases TNF-α |
author_facet |
Ningyuan Wang Yan Huang An Li Hailong Jiang Jie Wang Jianzhong Li Lei Qiu Ka Li Yiming Lu |
author_sort |
Ningyuan Wang |
title |
Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea |
title_short |
Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea |
title_full |
Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea |
title_fullStr |
Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea |
title_full_unstemmed |
Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea |
title_sort |
hydrostatin-tl1, an anti-inflammatory active peptide from the venom gland of hydrophis cyanocinctus in the south china sea |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2016-11-01 |
description |
Tumor necrosis factor (TNF)-α is a pleiotropic cytokine with intense pro-inflammatory and immunomodulatory properties, and anti-TNF-α biologics are effective therapies for various inflammatory diseases such as inflammatory bowel disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has been used in the treatment of inflammatory diseases in China for centuries. In this research, we constructed a venom gland T7 phage display library of the sea snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF-α and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H-TL1). In enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analyses, H-TL1 inhibited the interaction between TNF-α and TNF receptor 1 (TNFR1). Further, H-TL1 attenuated the cytotoxicity of TNF-α in L929 cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. H-TL1 also decreased the mRNA expression of TNF-α/TNFR1 downstream targets and suppressed the phosphorylation of well-characterized proteins of downstream signal transduction pathways in HEK-293 cells. In vivo data demonstrated that H-TL1 protects animals against dextran sodium sulfate (DSS)-induced acute colitis and lipopolysaccharide (LPS)-induced acute shock. Given its significant anti-inflammatory activity in vitro and in vivo, H-TL1 is a potential peptide for the development of new agents to treat TNF-α-associated inflammatory diseases. |
topic |
H-TL1 Hydrophis cyanocinctus anti-inflammatory inflammatory bowel diseases TNF-α |
url |
http://www.mdpi.com/1422-0067/17/11/1940 |
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