title: Tityus serrulatus venom and toxins Ts1, Ts2 and Ts6 induce macrophage activation and production of immune mediators.
abstract: Scorpion envenomation induces a systemic immune response, and neurotoxins of venom act on specific ion channels, modulating neurotransmitter release or activity. However, little is known about the immunomodulatory effects of crude venom from scorpion Tityus serrulatus (TsV) or its toxins (Ts1, Ts2 and Ts6) in combination with lipopolysaccharide (LPS). To investigate the immunomodulatory effects of TsV and its toxins (Ts1, Ts2 and Ts6), J774.1 cells were stimulated with different concentrations (25, 50 and 100 μg/mL) of venom or toxins pre-stimulated or not with LPS (0.5 μg/mL). Macrophage cytotoxicity was assessed, and nitric oxide (NO) and cytokine production were analyzed utilizing the culture supernatants. TsV and its toxins did not produce cytotoxic effects. Depending on the concentrations used, TsV, Ts1 and Ts6 stimulated the production of NO, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in J774.1 cells, which were enhanced under LPS co-stimulation. However, LPS + Ts2 inhibited NO, IL-6 and TNF-α production, and Ts2 alone stimulated the production of IL-10, suggesting an anti-inflammatory activity for this toxin. Our findings are important for the basic understanding of the mechanisms involved in macrophage activation following envenomation; additionally, these findings may contribute to the discovery of new therapeutic compounds to treat immune-mediated diseases.
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, CEP 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: Adriana
authors.initials: A
authors.lastname: Secatto
authors.forename: Carlos Artério
authors.initials: CA
authors.lastname: Sorgi
authors.forename: Karla de Castro Figueredo
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; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007154:Immune System Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009498:Neurotoxins; D012604:Scorpion Venoms; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide