Macrophages from a type 1 diabetes mouse model present dysregulated Pl3K/AKT, ERK 1/2 and SAPK/JNK levels.

Autor: Galvão Tessaro FH; Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences - University of Sao Paulo (FCF/USP), São Paulo, Brazil., Ayala TS; Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences - University of Sao Paulo (FCF/USP), São Paulo, Brazil., Bella LM; Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences - University of Sao Paulo (FCF/USP), São Paulo, Brazil., Martins JO; Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences - University of Sao Paulo (FCF/USP), São Paulo, Brazil. Electronic address: martinsj@usp.br.
Jazyk: angličtina
Zdroj: Immunobiology [Immunobiology] 2020 Mar; Vol. 225 (2), pp. 151879. Date of Electronic Publication: 2019 Nov 30.
DOI: 10.1016/j.imbio.2019.11.014
Abstrakt: 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 signal-regulated kinases (ERK 1/2), and stress-activated protein kinase (SAPK/JNK) were enhanced compared to non-diabetic 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)-α, 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-α 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.
(Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
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