ArticleMolecular and cellular biochemistry2011
Anti-inflammatory effect of insulin in the human hepatoma cell line HepG2 involves decreased transcription of IL-6 target genes and nuclear exclusion of FOXO1.
Article in Molecular and cellular biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination.International journal of biological sciences · 2022Article
- Serum- and Glucocorticoid-Inducible Kinase 1 Promotes Alternative Macrophage Polarization and Restrains Inflammation through FoxO1 and STAT3 Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Mechanism by Which Amentoflavone Improves Insulin Resistance in HepG2 Cells.Molecules (Basel, Switzerland) · 2016Article
- FOXO1 involvement in insulin resistance-related pro-inflammatory cytokine production in hepatocytes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2012Article
- Markers, Pathways, and Current Evidence for Periodontitis-associated Insulin Resistance: A Narrative Review.Journal of International Society of Preventive & Community DentistryReview
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
The liver is an important target for interleukin-6 (IL-6) action leading to an increased inflammatory response with impaired insulin signaling and action. The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction. It was found that insulin significantly reduced IL-6-induced gene transcription of serum amyloid 1 (SAA1), serum amyloid 2 (SAA2), haptoglobin, orosomucoid, and plasmin activator inhibitor-1 (PAI-1). However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus. The potential role of PKCδ was also analyzed but no evidence of its involvement was found. Taken together, these results suggest that the anti-inflammatory effect of insulin on IL-6 action is exerted at the level of the transcriptional activation of the genes. Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription. Insulin induced nuclear exit and Thr24 phosphorylation of FOXO1, thus, inhibiting STAT3-mediated transcription.
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