Cross-talk between insulin signalling and LPS responses in mouse macrophages. (15th November 2018)

• Record Type: Journal Article
• Authors: Pal, Soumojit; Nath, Poulomi; Das, Debabrata; Hajra, Sudip; Maitra, Sudipta
• Is Part Of: Molecular and cellular endocrinology. Volume 476(2018)
• Page Start: 57
• Page End: 69
• Publication Date: 2018-11-15
• Subjects: Il-10 -- Tnf-α -- NF-κB -- ERK1/2 -- Macrophage -- Insulin; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.04.009
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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. Highlights: 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.