title: Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of Hydrophis cyanocinctus in the South China Sea.
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 snakeHydrophis cyanocinctusto 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.
authors.affiliation: School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China. wangningyuan1230@163.com.
authors.forename: Ningyuan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. huangyantiger2005@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. ezioleon@foxmail.com.
authors.forename: An
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. jhlong1986@163.com.
authors.forename: Hailong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. wj890801@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. lijianzhong1234@hotmail.com.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. qlcong021@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China. karllee75@hotmail.com.
authors.forename: Ka
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. bluesluyi@sina.com.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017812:Colubridae / Q000378:metabolism; D016264:Dextran Sulfate; D004546:Elapid Venoms / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000737:chemistry / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008070:Lipopolysaccharides; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D019151:Peptide Library; D010766:Phosphorylation; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D030162:Reptilian Proteins / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D012910:Snake Venoms / Q000737:chemistry* / Q000302:isolation & purification; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D004546:Elapid Venoms; D008070:Lipopolysaccharides; D009842:Oligopeptides; D019151:Peptide Library; D047888:Receptors, Tumor Necrosis Factor, Type I; D030162:Reptilian Proteins; D012910:Snake Venoms; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; C000616593:hydrostatin-TL1 peptide, Hydrophis cyanocinctus; D016264:Dextran Sulfate; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: H-TL1; Hydrophis cyanocinctus; TNF-α; anti-inflammatory; inflammatory bowel diseases