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Investigating the role of insulin in the presence of allergic pulmonary inflammation in diabetic and healthy mice

Grant number: 17/11540-7
Support type:Regular Research Grants
Duration: February 01, 2018 - January 31, 2020
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Joilson de Oliveira Martins
Grantee:Joilson de Oliveira Martins
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated grant(s):18/50004-6 - Mechanisms linking angiotensins to obesity and Diabetes: role of inflammation, endoplasmic reticulum stress and autophagy, AP.R SPRINT

Abstract

Asthma is a complex disease that simultaneously involves the participation of several cells, cytokines and inflammatory mediators on which the initial phase is completely different from the late stage. In previous work, we used an experimental omdel developen in mice pre-immunized with ovalbumin (OVA) and found that insulin interferes with the production/release of cytokines, cell migration, collagen deposition and mucus secretion in pulmonary remodeling of a murine asthma model. The asthma model proposed in this project uses a booster dose of antigen twelve days after the first immunization and following, the animals are subjected to seven subsequently antigenic challenges. This model is characterized by a specific pattern of inflammation in the airway mucosa, involving eosinophils with a predominantly lymphocytes subpopulation of T helper (Th)2. Furthermore, structural changes occurring in the airways (remodeling) are observed, including increased collagen deposition around the bronchial sub-epithelial fibrosis, hyperplasia and hypertrophy of smooth muscle of the airways, angiogenesis, and increased mucus secretion. With this additional grant, we aim to assess the modulatory role of insulin in pulmonary inflammation. The study performed in healthy mice will be transferred to diabetic mice and molecular basis of inflammation will be targeted. The study will include: a) glucose levels; b) study of airway responsiveness after bronchial provocation by methylcholine (buxco), and assessment of respiratory function (flexiVent) c) study of cells present in bronchoalveolar lavage (BAL), as well as analysis of cell subpopulations by flow cytometry in samples from the bone marrow, lung, thymus and spleen; d) determination of serum levels of: insulin, corticosterone and immunoglobulins (IgE, IgG1 and IgG2a) by ELISA; e) cytokines concentration in BAL supernatant samples by ELISA (IL-4, IL-5, IL-10, IL-13, TNF-± and IFN-³); f) expression of the molecules involved in cell signalling pathways (p38 MAPK, collagen I, Smad 2 and Smad 3) in the lungs and bone marrow by Western blot g) alterations in the m-RNA expression by RT-PCR in the intracellular signaling pathways during the course of allergic inflammation. (AU)

Scientific publications (9)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GALVAO TESSARO, FERNANDO HENRIQUE; AYALA, THAIS SOPRANI; BELLA, LEONARDO MENDES; MARTINS, JOILSON OLIVEIRA. Macrophages from a type 1 diabetes mouse model present dysregulated P13K/AKT, ERK 1/2 and SAPK/JNK levels. Immunobiology, v. 225, n. 2 MAR 2020. Web of Science Citations: 0.
FERREIRA, SABRINA S.; OLIVEIRA, MARIA A.; TSUJITA, MARISTELA; NUNES, FERNANDA P. B.; CASAGRANDE, FELIPE B.; GOMES, ELIANE; RUSSO, MOMTCHILO; TAVARES DE LIMA, WOTHAN; MARTINS, JOILSON O. Insulin Modulates the Immune Cell Phenotype in Pulmonary Allergic Inflammation and Increases Pulmonary Resistance in Diabetic Mice. FRONTIERS IN IMMUNOLOGY, v. 11, FEB 11 2020. Web of Science Citations: 0.
AYALA, THAIS SOPRANI; GALVAO TESSARO, FERNANDO HENRIQUE; JANNUZZI, GRASIELLE PEREIRA; BELLA, LEONARDO MENDES; FERREIRA, KAREN SPADARI; MARTINS, JOILSON O. High Glucose Environments Interfere with Bone Marrow-Derived Macrophage Inflammatory Mediator Release, the TLR4 Pathway and Glucose Metabolism. SCIENTIFIC REPORTS, v. 9, AUG 7 2019. Web of Science Citations: 0.
BARROS, MICHELE S.; LARA, PRISCILA G.; FONSECA, MONIQUE T.; MORETTI, EDUARDO H.; FILGUEIRAS, LUCIANO R.; MARTINS, JOILSON O.; CAPURRO, MARGARETH L.; STEINER, ALEXANDRE A.; SA-NUNES, ANDERSON. Aedes aegypti saliva impairs M1-associated proinflammatory phenotype without promoting or affecting M2 polarization of murine macrophages. PARASITES & VECTORS, v. 12, MAY 16 2019. Web of Science Citations: 1.
KNOX DE SOUZA, PAULA R.; FERREIRA, SABRINA S.; NUNES, FERNANDA P. B.; CASAGRANDE, FELIPE B.; TESSARO, FERNANDO H. G.; SILVA, MARIANA C. F.; MIRANDA COSTA CRUZ, JOSE WALBER; MAMIZUKA, ELSA M.; MARTINS, JOILSON O. Cytokine and Adhesion Molecule Expression Induced by Different Strains of Staphylococcus aureus in Type 1 Diabetic Rats: Role of Insulin. FRONTIERS IN IMMUNOLOGY, v. 9, JAN 17 2019. Web of Science Citations: 0.
GUIMARAES, JOAO PEDRO TORRES; FILGUEIRAS, LUCIANO RIBEIRO; MARTINS, JOILSON OLIVEIRA; JANCAR, SONIA. Leukotriene Involvement in the Insulin Receptor Pathway and Macrophage Profiles in Muscles from Type 1 Diabetic Mice. Mediators of Inflammation, 2019. Web of Science Citations: 0.
RAJASEKARAN, SUBU SURENDRAN; KIM, JAEYOON; GABOARDI, GIAN-CARLO; GROMADA, JESPER; SHEARS, STEPHEN B.; DOS SANTOS, KAREN TIAGO; NOLASCO, EDUARDO LIMA; FERREIRA, SABRINA DE SOUZA; ILLIES, CHRISTOPHER; KOHLER, MARTIN; GU, CHUNFANG; RYU, SUNG HO; MARTINS, JOILSON O.; DARE, ELISABETTA; BARKER, CHRISTOPHER J.; BERGGREN, PER-OLOF. Inositol hexakisphosphate kinase 1 is a metabolic sensor in pancreatic beta-cells. CELLULAR SIGNALLING, v. 46, p. 120-128, JUN 2018. Web of Science Citations: 3.
CASAGRANDE, FELIPE BECCARIA; FERREIRA, SABRINA DE SOUZA; BARBOSA NUNES, FERNANDA PEIXOTO; DAL'MAS ROMERA, LAVINIA MARIA; DOS SANTOS, SUELEN SILVANA; GALVAO TESSARO, FERNANDO HENRIQUE; KNOX DE SOUZA, PAULA REGINA; ALMEIDA, SANDRO ROGERIO; MARTINS, JOILSON OLIVEIRA. Insulin Modulates Paracoccidioides brasiliensis-Induced Inflammation by Restoring the Populations of NK Cells, Dendritic Cells, and B Lymphocytes in Lungs. JOURNAL OF DIABETES RESEARCH, 2018. Web of Science Citations: 0.
MENDES-BRAZ, MARIANA; MARTINS, JOILSON O. Diabetes Mellitus and Liver Surgery: The Effect of Diabetes on Oxidative Stress and Inflammation. Mediators of Inflammation, 2018. Web of Science Citations: 4.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.