Cross-talk between insulin signalling and LPS responses in mouse macrophages

• Published in: Molecular and cellular endocrinology 2018-11, Vol.476, p.57-69
• Main Authors: Pal, Soumojit, Nath, Poulomi, Das, Debabrata, Hajra, Sudip, Maitra, Sudipta
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Cyclic AMP Response Element-Binding Protein - metabolism; Cytokines - genetics; Cytokines - metabolism; ERK1/2; Gene Expression Regulation - drug effects; Glucose - toxicity; Il-10; Inflammation - pathology; Inflammation Mediators - metabolism; Insulin; Insulin - metabolism; Insulin - pharmacology; Lipopolysaccharides - pharmacology; Macrophage; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Male; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; NF-κB; RAW 264.7 Cells; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Tnf-α
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2018.04.009

The effect of insulin priming on Il-10 expression, regulation of inflammatory cytokines and participation of intra-cellular signalling events, primarily ERK1/2 and PI3K/Akt, has been investigated in high glucose (HG) and/or lipopolysaccharide (LPS)-induced murine macrophages. Our results demonstrate that congruent with sharp increase in ERK1/2 and CREB phosphorylation, insulin stimulation in vitro promotes significant increase in Il-10 expression in mouse peritoneal macrophage and RAW 264.7 cells, both positive for anti-IRβ. Pharmacological inhibition of MEK/MAPK, but not PI3K/Akt cascade, abrogates CREB phosphorylation and Il-10 synthesis indicating functional relevance of insulin action. Conversely, priming with PI3K inhibitor wortmannin prevents insulin attenuation of HG- and/or LPS-induced p38 MAPK and NF-κB activation, Tnf-α, Il-1β expression as well as NO production. Congruent with reduced Il-10 expression, MEK inhibition abrogates insulin action allowing significant increase in Tlr4 expression and LPS response indicating insulin-induced Il-10 might have pivotal influence in regulation of chronic as well as acute inflammatory response. •Insulin promotes Il-10 expression in mouse macrophages; positive for anti-IRβ•Elevated Il-10 expression involves ERK1/2 and CREB but not PI3K/Akt activation.•Insulin attenuates HG and/or LPS-induced Tnf-α, Il-1β, inos mRNA and NO synthesis.•Insulin priming attenuates TLR4 expression and LPS-induced NF-κB, p38 MAPK activation.•PI3K inhibitor prevents insulin blocking of LPS-induced inflammation.