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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Macrophages from a type 1 diabetes mouse model present dysregulated P13K/AKT, ERK 1/2 and SAPK/JNK levels

Full text
Author(s):
Galvao Tessaro, Fernando Henrique [1] ; Ayala, Thais Soprani [1] ; Bella, Leonardo Mendes [1] ; Martins, Joilson Oliveira [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo FCF USP, Dept Clin & Toxicol Anal, Lab Immunoendocrinol, Sch Pharmaceut Sci, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Immunobiology; v. 225, n. 2 MAR 2020.
Web of Science Citations: 0
Abstract

Diabetes causes dysregulation in signal transduction in immune cells leading to an impaired response to pathogens. Herein, we investigated the impact of type 1 diabetes (T1D) in bone marrow-derived macrophages (BMDM), using male non-diabetic and diabetic C57BL/6 mice (alloxan 60 mg/kg, i.v., CEUA/FCF/USP - 467). Diabetic BMDM expressed impaired phosphoinositide 3-kinase (PI3K), being lower p-PI3K p55 levels and higher levels of PI3K p110 alpha, whereas protein kinase B (PKB/Akt) (Ser-473 and Thr-308), extracellular signalregulated kinases (ERK 1/2), and stress-activated protein kinase (SAPK/JNK) were enhanced compared to nondiabetic BMDM. Further evaluation of the responsiveness to lipopolysaccharide (LPS; 0.1 and 1 ug/mL), diabetic BMDM and peritoneal macrophage secreted dysregulated levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels. In 24 h, diabetic BMDM stimulated by LPS presented lower metabolic activity, with no differences in cell surveillance. Therefore, LPS re-stimulation (0.1 ug/mL) in diabetic BMDM resulted in higher secretion of TNF-alpha compared to non-diabetic BMDM. However, diabetic peritoneal macrophages secreted similar IL-6 levels in the first and additional 24 h of LPS stimulation. In general, our results demonstrated that diabetes exerts an impact in both BMDM and peritoneal macrophages ability to secrete cytokine under LPS stimulation. (AU)

FAPESP's process: 14/05214-1 - Investigating the role of insulin in different infections in diabetic and healthy animals
Grantee:Joilson de Oliveira Martins
Support Opportunities: Regular Research Grants
FAPESP's process: 17/11540-7 - Investigating the role of insulin in the presence of allergic pulmonary inflammation in diabetic and healthy mice
Grantee:Joilson de Oliveira Martins
Support Opportunities: Regular Research Grants
FAPESP's process: 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
Grantee:Joilson de Oliveira Martins
Support Opportunities: Research Grants - Young Investigators Grants