Insulin enhances dendritic cell maturation and scavenger receptor-mediated uptake of oxidised low-density lipoprotein
- PMID: 25813675
- DOI: 10.1016/j.jdiacomp.2015.03.005
Insulin enhances dendritic cell maturation and scavenger receptor-mediated uptake of oxidised low-density lipoprotein
Abstract
Objectives: The prevalence of atherosclerotic cardiovascular disease is increased in patients with type 2 diabetes. The role of hyperinsulinaemia as an independent participant in the atherogenic process is controversial. Therefore, we examined whether insulin regulates the expression of scavenger receptors responsible for oxidised low-density lipoprotein (oxLDL) uptake in dendritic cells (DCs). In addition, we investigated the impact of insulin on DC maturation with regard to changes in phenotype and cytokine secretion.
Methods: Immature DCs were cultured with different concentrations of insulin (1nmol/L, 10nmol/L, 50nmol/L, and 100nmol/L) in the absence or presence of LY294002 or PD98059 for 24h. The expression of the scavenger receptors SR-A and CD36 was determined by real-time PCR and Western blot analysis. Furthermore, DCs were incubated with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labelled oxLDL. The DiI-oxLDL-incorporated fraction was investigated by flow cytometry. Finally, flow cytometry was used to investigate immunophenotypic protein expression (CD83, CD86, and CD11a). Supernatant cytokine measurements were used as indicators of immune function.
Results: The incubation of DCs with insulin enhanced SR-A and CD36 gene and protein expression in a dose-dependent manner. This effect was partially abolished by PD98059, which is an extracellular signal-regulated kinase (ERK) inhibitor. However, LY294002 did not inhibit the effect of insulin on scavenger receptor expression. A high concentration of insulin increased the oxLDL-uptake capacity of DCs. Inhibition of the scavenger receptors SR-A and CD36 significantly reduced oxLDL uptake. Furthermore, a high concentration of insulin induced DC maturation. The pro-atherosclerotic chemokines IL-6 and IL-12 were induced by a high concentration of insulin, whereas the release of anti-atherosclerotic IL-10 was reduced.
Conclusion: This study suggests that hyperinsulinaemia can promote DC activation and up-regulate the expression of the scavenger receptors SR-A and CD36, which can increase the oxLDL-uptake capacity of DCs. The results of the present study indicate that one of the mechanisms by which insulin promotes atherogenesis is mediated by its effects on DCs.
Keywords: Atherosclerosis; Dendritic cell; Hyperinsulinaemia; Scavenger receptors; Type 2 diabetes.
Copyright © 2015 Elsevier Inc. All rights reserved.
Similar articles
-
High glucose induces upregulation of scavenger receptors and promotes maturation of dendritic cells.Cardiovasc Diabetol. 2013 May 29;12:80. doi: 10.1186/1475-2840-12-80. Cardiovasc Diabetol. 2013. PMID: 23718574 Free PMC article.
-
oxLDL uptake by dendritic cells induces upregulation of scavenger-receptors, maturation and differentiation.Atherosclerosis. 2009 Aug;205(2):442-50. doi: 10.1016/j.atherosclerosis.2009.01.002. Epub 2009 Jan 9. Atherosclerosis. 2009. PMID: 19203752
-
Dioscin attenuates oxLDL uptake and the inflammatory reaction of dendritic cells under high glucose conditions by blocking p38 MAPK.Mol Med Rep. 2020 Jan;21(1):304-310. doi: 10.3892/mmr.2019.10806. Epub 2019 Nov 6. Mol Med Rep. 2020. PMID: 31746382 Free PMC article.
-
[The influence of diabetes mellitus and insulin resistance on receptor CD36 expression. Part II. The role of receptor CD36 in the pathomechanism of diabetes complications].Postepy Hig Med Dosw (Online). 2006;60:152-62. Postepy Hig Med Dosw (Online). 2006. PMID: 16552395 Review. Polish.
-
Scavenger receptor-A (CD204): a two-edged sword in health and disease.Crit Rev Immunol. 2014;34(3):241-61. doi: 10.1615/critrevimmunol.2014010267. Crit Rev Immunol. 2014. PMID: 24941076 Free PMC article. Review.
Cited by
-
Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge.Front Immunol. 2023 Nov 23;14:1323439. doi: 10.3389/fimmu.2023.1323439. eCollection 2023. Front Immunol. 2023. PMID: 38077372 Free PMC article. Review.
-
Identification of ferroptosis-related genes in type 2 diabetes mellitus based on machine learning.Immun Inflamm Dis. 2023 Oct;11(10):e1036. doi: 10.1002/iid3.1036. Immun Inflamm Dis. 2023. PMID: 37904700 Free PMC article.
-
Dendritic cell-mediated chronic low-grade inflammation is regulated by the RAGE-TLR4-PKCβ1 signaling pathway in diabetic atherosclerosis.Mol Med. 2022 Jan 21;28(1):4. doi: 10.1186/s10020-022-00431-6. Mol Med. 2022. PMID: 35062863 Free PMC article.
-
Regulation of the immune system by the insulin receptor in health and disease.Front Endocrinol (Lausanne). 2023 Mar 13;14:1128622. doi: 10.3389/fendo.2023.1128622. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 36992811 Free PMC article. Review.
-
Quantitative Phosphoproteomic Analysis Reveals Dendritic Cell- Specific STAT Signaling After α2-3-Linked Sialic Acid Ligand Binding.Front Immunol. 2021 Apr 22;12:673454. doi: 10.3389/fimmu.2021.673454. eCollection 2021. Front Immunol. 2021. PMID: 33968084 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous