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Article

Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea

by
Ningyuan Wang
1,†,
Yan Huang
2,†,
An Li
2,†,
Hailong Jiang
2,
Jie Wang
2,
Jianzhong Li
2,
Lei Qiu
2,
Ka Li
3,* and
Yiming Lu
2,*
1
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
2
Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
3
Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2016, 17(11), 1940; https://doi.org/10.3390/ijms17111940
Submission received: 22 September 2016 / Revised: 31 October 2016 / Accepted: 14 November 2016 / Published: 22 November 2016
(This article belongs to the Section Biochemistry)
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Abstract

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.
Keywords: H-TL1; Hydrophis cyanocinctus; anti-inflammatory; inflammatory bowel diseases; TNF-α H-TL1; Hydrophis cyanocinctus; anti-inflammatory; inflammatory bowel diseases; TNF-α
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MDPI and ACS Style

Wang, N.; Huang, Y.; Li, A.; Jiang, H.; Wang, J.; Li, J.; Qiu, L.; Li, K.; Lu, Y. Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea. Int. J. Mol. Sci. 2016, 17, 1940. https://doi.org/10.3390/ijms17111940

AMA Style

Wang N, Huang Y, Li A, Jiang H, Wang J, Li J, Qiu L, Li K, Lu Y. Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea. International Journal of Molecular Sciences. 2016; 17(11):1940. https://doi.org/10.3390/ijms17111940

Chicago/Turabian Style

Wang, Ningyuan, Yan Huang, An Li, Hailong Jiang, Jie Wang, Jianzhong Li, Lei Qiu, Ka Li, and Yiming Lu. 2016. "Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea" International Journal of Molecular Sciences 17, no. 11: 1940. https://doi.org/10.3390/ijms17111940

APA Style

Wang, N., Huang, Y., Li, A., Jiang, H., Wang, J., Li, J., Qiu, L., Li, K., & Lu, Y. (2016). Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea. International Journal of Molecular Sciences, 17(11), 1940. https://doi.org/10.3390/ijms17111940

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