title: From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide.
abstract: The primary purpose of the present study was to investigate the mechanism of the counter-irritating activity of topical iodine against skin lesions induced by chemical and thermal stimuli. The hypothesis that iodine exerts its activity by inducing an endogenous anti-inflammatory factor was confirmed by exposing guinea pig skin to heat stimulus followed by topical iodine treatment and skin extraction. Injection of the extract into naïve guinea pigs reduced heat-induced irritation by 69%. The protective factor, identified as a new nonapeptide (histone H2A 36-44, H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH), caused reduction of 40% in irritation score in heat-exposed guinea pigs. The murine analog (H-Lys-Gly-His-Tyr-Ala-Glu-Arg-Val-Gly-OH, termed IIIM1) reduced sulfur mustard (SM)-induced ear swelling at a dose-dependent bell-shape manner reaching peak activity of 1 mg/kg. Cultured keratinocytes transfected with the peptide were more resistant towards SM than the control cells. The peptide suppressed oxidative burst in activated neutrophils in a concentration-dependent manner. In addition, the peptide reduced glucose oxidase-induced skin edema in mice at a dose-dependent bell-shape manner. Apart from thermal and chemical-induced skin irritation this novel peptide might be of potential use in chronic dermal disorders such as psoriasis and pemphigus as well as non-dermal inflammatory diseases like multiple sclerosis, arthritis and colitis.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Institute of Life Sciences, The Hebrew University, 91120 Jerusalem, Israel.
authors.forename: Berta
authors.initials: B
authors.lastname: Brodsky
authors.forename: Avigail
authors.initials: A
authors.lastname: Erlanger-Rosengarten
authors.forename: Elena
authors.initials: E
authors.lastname: Proscura
authors.forename: Elena
authors.initials: E
authors.lastname: Shapira
authors.forename: Uri
authors.initials: U
authors.lastname: Wormser
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006657:Histones / Q000378:metabolism*; D006358:Hot Temperature / Q000009:adverse effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009151:Mustard Gas / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments; D011206:Povidone-Iodine / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D016897:Respiratory Burst / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D023422:Skin Irritancy Tests; D013373:Substance P / Q000378:metabolism; D014162:Transfection
chemical_list: D000891:Anti-Infective Agents, Local; D006657:Histones; D009842:Oligopeptides; D010446:Peptide Fragments; D020011:Protective Agents; C530140:lysyl-glycyl-histidyl-tyrosyl-alanyl-glutamyl-arginyl-valyl-glyine; D013373:Substance P; D011206:Povidone-Iodine; D009151:Mustard Gas