title: Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms dependent on lipid mediators and cytokine production.
abstract: Inflammatory mediators are thought to be involved in the systemic and local immune response induced by the Tityus serrulatus scorpion envenomation. New functional aspects of lipid mediators have recently been described. Here, we examine the unreported role of lipid mediators in cell recruitment to the peritoneal cavity after an injection with Ts2 or Ts6 toxins isolated from the T. serrulatus scorpion venom. In this report, we demonstrate that following a single intraperitoneal (i.p.) injection of Ts2 or Ts6 (250 μg/kg) in mice, there was an induction of leukocytosis with a predominance of neutrophils observed at 4, 24, 48 and 96 h. Moreover, total protein, leukotriene (LT)B(4), prostaglandin (PG)E(2) and pro-inflammatory cytokine levels were increased. We also observed an increase of regulatory cytokines, including interleukin (IL)-10, after the Ts2 injection. Finally, we observed that Ts2 or Ts6 injection in 5-lipoxygenase (LO) deficient mice and in wild type (WT) 129sv mice pre-treated with LTs and PGs inhibitors (MK-886 and celecoxib, respectively) a reduction the influx of leukocytes occurs in comparison to WT. The recruitment of these cells demonstrated a phenotype characteristic of neutrophils, macrophages, CD4 and CD8 lymphocytes expressing GR1+, F4/80+, CD3+/CD4+ and CD3+/CD8+, respectively. In conclusion, our data demonstrate that Ts2 and Ts6 induce inflammation by mechanisms dependent on lipid mediators and cytokine production. Ts2 may play a regulatory role whereas Ts6 exhibits pro-inflammatory activity exclusively.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil. karina_zoccal4@hotmail.com
authors.forename: Karina Furlani
authors.initials: KF
authors.lastname: Zoccal
authors.forename: Claudia da Silva
authors.initials: Cda S
authors.lastname: Bitencourt
authors.forename: Carlos Artério
authors.initials: CA
authors.lastname: Sorgi
authors.forename: Karla de Castro Figueiredo
authors.initials: Kde C
authors.lastname: Bordon
authors.forename: Suely Vilela
authors.initials: SV
authors.lastname: Sampaio
authors.forename: Eliane Candiani
authors.initials: EC
authors.lastname: Arantes
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D000068579:Celecoxib; D002465:Cell Movement / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology*; D007962:Leukocytes / Q000187:drug effects; D015289:Leukotrienes / Q000096:biosynthesis / Q000502:physiology; D008055:Lipids / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D010529:Peritoneal Cavity / Q000473:pathology; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D012604:Scorpion Venoms / Q000633:toxicity*; D013449:Sulfonamides / Q000494:pharmacology; D002722:Chlorobenzenes
chemical_list: D001094:Arachidonate 5-Lipoxygenase; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D007211:Indoles; D018836:Inflammation Mediators; D015289:Leukotrienes; D008055:Lipids; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; D012604:Scorpion Venoms; D013449:Sulfonamides; C581453:Ts2 toxin, Tityus serrulatus; C581454:Ts6 toxin, Tityus serrulatus; C060893:MK-886; D002722:Chlorobenzenes