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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Insulin Modulates the Immune Cell Phenotype in Pulmonary Allergic Inflammation and Increases Pulmonary Resistance in Diabetic Mice

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Autor(es):
Ferreira, Sabrina S. [1] ; Oliveira, Maria A. [2] ; Tsujita, Maristela [3] ; Nunes, Fernanda P. B. [1] ; Casagrande, Felipe B. [1] ; Gomes, Eliane [4] ; Russo, Momtchilo [4] ; Tavares de Lima, Wothan [2] ; Martins, Joilson O. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo FCF USP, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Lab Immunoendocrinol, Sao Paulo - Brazil
[2] Univ Sao Paulo ICB USP, Inst Biomed Sci, Dept Pharmacol, Lab Physiopathol Expt Lung Inflammat, Sao Paulo - Brazil
[3] Univ Sao Paulo FCF USP, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Hematol Lab, Sao Paulo - Brazil
[4] Univ Sao Paulo ICB USP, Inst Biomed Sci, Dept Immunol, Immunobiol Lab, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN IMMUNOLOGY; v. 11, FEB 11 2020.
Citações Web of Science: 0
Resumo

Introduction: Reports have shown that the onset of diabetes mellitus (DM) in patients previously diagnosed with asthma decreases asthmatic symptoms, whereas insulin aggravates asthma. The present study evaluated the modulatory effect of insulin on the development of allergic airway inflammation in diabetic mice. Materials and Methods: To evaluate the effects of relative insulin deficiency, an experimental model of diabetes was induced by a single dose of alloxan (50 mg/kg, i.v.). After 10 days, the mice were sensitized with ovalbumin {[}OVA, 20 mu g and 2 mg of Al(OH)(3), i.p.]. A booster immunization was performed 6 days after the first sensitization {[}20 mu g of OVA and 2 mg of Al(OH)(3), i.p.]. The OVA challenge (1 mg/mL) was performed by daily nebulization for 7 days. Diabetic animals were treated with multiple doses of neutral protamine Hagedorn (NPH) before each challenge with OVA. The following parameters were measured 24 h after the last challenge: (a) the levels of p38 MAP kinase, ERK 1/2 MAP kinases, JNK, STAT 3, and STAT 6 in lung homogenates; (b) the serum profiles of immunoglobulins IgE and IgG1; (c) the concentrations of cytokines (IL-4, IL-5, IL-10, IL-13, TNF-alpha, VEGF, TGF-beta, and IFN-gamma) in lung homogenates; (d) cells recovered from the bronchoalveolar lavage fluid (BALF); (e) the profiles of immune cells in the bone marrow, lung, thymus, and spleen; and (f) pulmonary mechanics using invasive (FlexiVent) and non-invasive (BUXCO) methods. Results: Compared to non-diabetic OVA-challenged mice, OVA-challenged diabetic animals showed decreases in ERK 1 (2-fold), ERK 2 (7-fold), JNK (phosphor-54) (3-fold), JNK/SAPK (9-fold), STAT3 (4-fold), the levels of immunoglobulins, including IgE (1-fold) and IgG1 (3-fold), cytokines, including Th2 profile cytokines such as IL-4 (2-fold), IL-5 (2-fold), IL-13 (4-fold), TNF-alpha (2-fold), VEGF (2-fold), and TGF-beta (2-fold), inflammatory infiltrates (14-fold), T cells, NK cells, B cells and eosinophils in the bone marrow, lung, thymus and spleen, and airway hyperreactivity. STAT6 was absent, and no eosinophilia was observed in BALF. Insulin treatment restored all parameters. Conclusion: The data suggested that insulin modulates immune cell phenotypes and bronchial hyperresponsiveness in the development of allergic airway inflammation in diabetic mice. (AU)

Processo FAPESP: 14/05214-1 - Investigando o papel da insulina em diferentes infecções em animais diabéticos e sadios
Beneficiário:Joilson de Oliveira Martins
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/11540-7 - Investigando o papel da insulina na vigência da inflamação alérgica pulmonar em camundongos diabéticos e sadios
Beneficiário:Joilson de Oliveira Martins
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 20/00194-3 - A insulina modula o fenótipo da célula imune na inflamação alérgica pulmonar e aumenta a resistência pulmonar em camundongos diabéticos
Beneficiário:Joilson de Oliveira Martins
Linha de fomento: Auxílio à Pesquisa - Publicações científicas - Artigo