Role of insulin in the effectiveness of allergic pulmonary inflammation in healthy or diabetic mice

• Grant number: 12/06617-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2013
• Effective date (End): February 28, 2015
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Joilson de Oliveira Martins
• Grantee: Sabrina de Souza Ferreira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 10/02272-0 - Effect of insulin on lung inflammation in animal with sepsis, innate immunit,activation of insulin gene (BGK) and insulin receptors (IR)-A and IR-B, AP.JP

Abstract

In previous work we found changes in the allergic lung allergic inflammation (early phase - six hours after a single challenge), such as cellular infiltration, cytokine production (TNF-alpha, IL-1beta and IL-10) and molecules adhesion were reduced in diabetic rats. Treatment of these animals with a single dose of insulin, corrects these alterations. However, asthma is a complex disorder that involves both the participation of several cells, cytokines and inflammatory mediators. In addition, the early phase is completely different from the late phase. The immunization model proposed in this design by Hogan et al. (1997), using a booster dose of antigen seven days after the first immunization the animals and subjected to two antigenic challenges also interleaved for seven days. This model (late phase) characterized by a specific pattern of inflammation in the airway mucosa, involving eosinophils and lymphocytes with a predominance of Th2 subpopulation. Furthermore, structural changes may occur in the airways (remodeling) including increased collagen deposition around the bronchi, sub-epithelial fibrosis, hypertrophy and hyperplasia of airway smooth muscle, increased angiogenesis and mucus secretion. Thus, this new project aims to assess the role of insulin in the presence of the late phase of allergic pulmonary inflammation in healthy and diabetic mice. For this purpose will be made the following analysis: a) the number of cells in the bronchoalveolar lavage (BAL), the leucocyte count and serum glucose (glucose meter), b) the concentrations of cytokines (IL1b, TNF-a, IL-6, IL- 4, IL-10, VEGF, TGF-b) in the supernatant BAL by ELISA c) infiltration of lymphocytes (CD4+, CD8+, NK1.1, and Tgd) in BAL by flow cytometry (FACS), d) deposition of collagen in lung tissue by morphometric analysis of histological sections stained with Picrosirius e) quantification of the presence of mucus in the bronchi by morphometric analysis of histological sections stained with periodic acid-Schiff and alcian blue (AB-PAS).

Scientific publications

(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)

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. (17/11540-7, 12/06652-7, 14/05214-1, 12/06617-7, 10/02272-0)

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, v. 2018, p. 11-pg., 2018-01-01. (10/02272-0, 12/06617-7, 17/11540-7, 12/06652-7, 14/05214-1)

FERREIRA, SABRINA S.; NUNES, FERNANDA P. B.; CASAGRANDE, FELIPE B.; MARTINS, JOILSON O.. Insulin Modulates Cytokine Release, Collagen and Mucus Secretion in Lung Remodeling of Allergic Diabetic Mice. FRONTIERS IN IMMUNOLOGY, v. 8, JUN 9 2017. (14/05214-1, 12/06617-7, 10/02272-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERREIRA, Sabrina de Souza. Role of insulin on the presence of the remodeling induced by allergic airway inflammation in healthy and diabetic mice. 2015. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.