Insulin Influences LPS-Induced TNF-α and IL-6 Release Through Distinct Pathways in Mouse Macrophages from Different Compartments
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-de...
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Veröffentlicht in: | Cellular physiology and biochemistry 2017-01, Vol.42 (5), p.2093-2104 |
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Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 1015-8987 1421-9778 |
DOI: | 10.1159/000479904 |