| Texto completo | |
| Autor(es): |
Tessaro, Fernando H. G.
[1]
;
Ayala, Thais S.
[1]
;
Nolasco, Eduardo L.
[1]
;
Bella, Leonardo M.
[1]
;
Martins, Joilson O.
[1]
Número total de Autores: 5
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo FCF USP, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Lab Immunoendocrinol, Sao Paulo - Brazil
Número total de Afiliações: 1
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CELLULAR PHYSIOLOGY AND BIOCHEMISTRY; v. 42, n. 5, p. 2093-2104, 2017. |
| Citações Web of Science: | 5 |
| Resumo | |
Background/Aims: Diabetic subjects are more susceptible to infections, which is partially due to insulin deficiency and hyperglycemia. We hypothesized that insulin influences cytokine release by macrophages from diabetic C57BL/6 mice stimulated with lipopolysaccharides (LPS). Methods: Bone marrow-derived macrophages (BMDM) and tissue-specific macrophages from diabetic (alloxan 60 mg/kg, i.v.) male C57BL/6 mice were stimulated by LPS (100 ng/mL) and/or treated by insulin (1 mU/mL). Results: Using BMDM from diabetic mice, we showed that LPS induced an increase in TNF-alpha and IL-6 release and p38, SAPK/JNK, ERK 1/2, and Akt (308-Thr and 473-Ser) phosphorylation but not in PKC alpha/beta II and delta. Insulin increased TNF-alpha and IL-6 secretion in LPS-stimulated macrophages as well as p-p38, p-SAPK/JNK, p-ERK 1/2, p-PI3K (p55) and p-Akt (473-Ser) expression. Furthermore, PI3-kinase inhibition by wortmannin decreased TNF-alpha release, and inhibition by LY294002 decreased both TNF-alpha and IL-6 levels after LPS-insulin treatment. PD98059, which inhibits the ERK upstream activators MAPK kinase (MKK) 1 and MKK2, reduced the effect promoted by insulin in BMDM stimulated by LPS In tissue-specific macrophages, insulin reduced LPS-induced TNF-alpha, IL-6 and IL-1 beta secretion in alveolar and peritoneal macrophages. Conclusion: These data suggest that insulin through the modulation of PI3-kinase and ERK 1/2 pathways drive different responses in macrophages, thereby enhancing our understanding of the plasticity of these cells. (C) 2017 The Author(s) Published by S. Karger AG, Basel (AU) | |
| Processo FAPESP: | 14/05214-1 - Investigando o papel da insulina em diferentes infecções em animais diabéticos e sadios |
| Beneficiário: | Joilson de Oliveira Martins |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 17/15625-7 - Insulin influences LPS-induced TNF-± and IL-6 release through distinct pathways in mouse macrophages from different compartments |
| Beneficiário: | Joilson de Oliveira Martins |
| Modalidade de apoio: | Auxílio à Pesquisa - Publicações científicas - Artigo |
| Processo FAPESP: | 12/23998-4 - Influência da vitamina D na expressão de receptores (VDR e TLR) em macrófagos no modelo de Diabetes Mellitus Experimental |
| Beneficiário: | Leonardo Mendes Bella |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 10/02272-0 - Efeito da insulina na inflamação pulmonar secundária a sepse, na imunidade inata, na ativação do seu gene (BGK) e seus receptores (IR-A e IR-B) |
| Beneficiário: | Joilson de Oliveira Martins |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |