title: Effects of P-MAPA immunomodulator on Toll-like receptor 2, ROS, nitric oxide, MAPKp38 and IKK in PBMC and macrophages from dogs with visceral leishmaniasis.
abstract: Leishmania (L.) chagasi is the etiologic agent of visceral leishmaniasis (VL) that can be transmitted to humans and dogs. VL in Brazil represents a serious public health problem; therefore, it is important to study new alternatives to treat infected dogs. In dogs, the therapeutic arsenal against canine VL is limited. The immunomodulator protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) improves immunocompetence when the immune system is impaired, but its dependence on Toll-like receptors (TLRs) and the mechanisms involved in immune response remain unclear. The in vitro action of P-MAPA on the expression of TLR2 and TLR4, reactive oxygen species (ROS), nitric oxide (NO) and p38 mitogen-activated protein kinase (p38 MAPK) and IKK phosphorylation was studied in mononuclear cells from peripheral blood and macrophages from healthy and Leishmania-infected dogs. The PBMC or macrophages were isolated and cultured with different concentrations of P-MAPA (20,100 and 200 μg/ml) in a humid environment at 37°C with 5% CO(2). Observation revealed that Leishmania-infected dogs showed a decrease in TLR2 in macrophages compared with healthy dogs and in induction with P-MAPA. ROS were increased in PBMCs from Leishmania spp.-infected dogs compared with healthy dogs and P-MAPA improved ROS production. NO production was increased in culture supernatant from macrophages stimulated by P-MAPA in both healthy and Leishmania spp. infected dogs. Treatment of macrophages from healthy dogs with immunomodulatory P-MAPA induced p38 MAPK and IKK phosphorylation, suggesting signal transduction by this pathway. These findings suggest that P-MAPA has potential as a therapeutic drug in the treatment of canine visceral leishmaniasis.
authors.affiliation: Pós-graduação em Ciência Animal, Faculdade de Medicina Veteinária, Universidade Estadual Paulista, Araçatuba, SP, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Melo
authors.affiliation: Pós-graduação em Ciência Animal, Faculdade de Medicina Veteinária, Universidade Estadual Paulista, Araçatuba, SP, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Perosso
authors.affiliation: Pós-graduação em Ciência Animal, Faculdade de Medicina Veteinária, Universidade Estadual Paulista, Araçatuba, SP, Brazil.
authors.forename: B F M
authors.initials: BF
authors.lastname: Almeida
authors.affiliation: Pós-graduação em Ciência Animal, Faculdade de Medicina Veteinária, Universidade Estadual Paulista, Araçatuba, SP, Brazil.
authors.forename: K L O
authors.initials: KL
authors.lastname: Silva
authors.affiliation: Departamento de Clínica, Cirugia e Reprodução Animal, Faculdade de Medicina Veterinária, Universidade Estadual Paulista, Araçatuba, SP, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Somenzari
authors.affiliation: Departamento de Clínica, Cirugia e Reprodução Animal, Faculdade de Medicina Veterinária, Universidade Estadual Paulista, Araçatuba, SP, Brazil. Electronic address: vmflima@fmva.unesp.br.
authors.forename: V M F
authors.initials: VM
authors.lastname: de Lima
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000276:immunology*; D004285:Dogs; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D051741:Kruppel-Like Transcription Factors / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000662:veterinary; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009569:Nitric Oxide / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D007155:Immunologic Factors; D051741:Kruppel-Like Transcription Factors; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Dog; Immunomodulatory; Leishmania sp.; P-MAPA; TLR