title: Aedes aegypti salivary gland extract ameliorates experimental inflammatory bowel disease.
abstract: Current therapies for inflammatory bowel disease (IBD) are not totally effective, resulting in persistent and recurrent disease for many patients. Mosquito saliva contains immunomodulatory molecules and therein could represent a novel therapy for IBD. Here, we demonstrated the therapeutic activity of salivary gland extract (SGE) of Aedes aegypti on dextran sulfate sodium (DSS)-induced colitis. For this purpose, C57BL/6 male mice were exposed to 3% DSS in drinking water and treated with SGE at early (days 3-5) or late (days 5-8) time points, followed by euthanasia on days 6 and 9, respectively, for sample collection. The results showed an improvement in clinical disease outcome and postmortem scores after SGE treatment, accompanied by the systemic reduction in peripheral blood lymphocytes, with no impact on bone marrow and mesenteric lymph nodes cellularity or macrophages toxicity. Moreover, a local diminishment of IFN-γ, TNF-α, IL-1β and IL-5 cytokines together with a reduction in the inflammatory area were observed in the colon of SGE-treated mice. Strikingly, early treatment with SGE led to mice protection from a late DSS re-challenging, as observed by decreased clinical and postmortem scores, besides reduced circulating lymphocytes, indicating that the mosquito saliva may present components able to prevent disease relapse. Indeed, high performance liquid chromatography (HPLC) experiments pointed to a major SGE pool fraction (F3) able to ameliorate disease signs. In conclusion, SGE and its components might represent a source of important immunomodulatory molecules with promising therapeutic activity for IBD.
authors.affiliation: Departamento de Análises Clínicas Toxicológicas e Bromatológicas-Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Helioswilton
authors.initials: H
authors.lastname: Sales-Campos
authors.affiliation: Departamento de Análises Clínicas Toxicológicas e Bromatológicas-Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Patricia Reis
authors.initials: PR
authors.lastname: de Souza
authors.affiliation: Departamento de Bioquímica e Imunologia-Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Paulo José
authors.initials: PJ
authors.lastname: Basso
authors.affiliation: Departamento de Imunologia-Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Anderson Daniel
authors.initials: AD
authors.lastname: Ramos
authors.affiliation: Departamento de Análises Clínicas Toxicológicas e Bromatológicas-Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Viviani
authors.initials: V
authors.lastname: Nardini
authors.affiliation: Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil.
authors.forename: Javier Emílio Lazo
authors.initials: JE
authors.lastname: Chica
authors.affiliation: Departamento de Parasitologia-Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Margareth Lara
authors.initials: ML
authors.lastname: Capurro
authors.affiliation: Departamento de Imunologia-Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Anderson
authors.initials: A
authors.lastname: Sá-Nunes
authors.affiliation: Departamento de Análises Clínicas Toxicológicas e Bromatológicas-Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. Electronic address: cristina@fcfrp.usp.br.
authors.forename: Cristina Ribeiro
authors.initials: CR
authors.lastname: de Barros Cardoso
mesh_terms: D000330:Aedes / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D012469:Salivary Glands / Q000737:chemistry*; D014020:Tissue Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D014020:Tissue Extracts; D016264:Dextran Sulfate
keywords: Aedes aegypti; Inflammatory bowel disease; Saliva; Therapy