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Insulin Influences LPS-Induced TNF-α and IL-6 Release Through Distinct Pathways in Mouse Macrophages from Different Compartments.

Insulin Influences LPS-Induced TNF-α and IL-6 Release Through Distinct Pathways in Mouse Macrophages from Different Compartments.
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Tessaro FHG, Ayala TS, Nolasco EL, Bella LM, Martins JO,


Tessaro FHG, Ayala TS, Nolasco EL, Bella LM, Martins JO, (click to view)

Tessaro FHG, Ayala TS, Nolasco EL, Bella LM, Martins JO,

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Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2017 08 1542(5) 2093-2104 doi 10.1159/000479904
Abstract
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-α and IL-6 release and p38, SAPK/JNK, ERK 1/2, and Akt (308-Thr and 473-Ser) phosphorylation but not in PKCα/β II and delta. Insulin increased TNF-α 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-α release, and inhibition by LY294002 decreased both TNF-α 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-α, IL-6 and IL-1β 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.

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