Role of Kir2.1 in human monocyte‐derived foam cell maturation

The role of K+ channels in macrophage immunomodulation has been well‐established. However, it remains unclear whether K+ channels are involved in the lipid uptake of macrophages. The expression and function of the inward rectifier potassium channel (Kir2.1, KCNJ2) in Human acute monocytic leukemia c...

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Main Authors: Zhang, Wei, Lei, Xin‐Jun, Wang, Yi‐Fan, Wang, Dong‐Qi, Yuan, Zu‐Yi
Format: Online
Language:English
Published: John Wiley and Sons Inc. 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759473/
id pubmed-4759473
recordtype oai_dc
spelling pubmed-47594732016-03-01 Role of Kir2.1 in human monocyte‐derived foam cell maturation Zhang, Wei Lei, Xin‐Jun Wang, Yi‐Fan Wang, Dong‐Qi Yuan, Zu‐Yi Original Articles The role of K+ channels in macrophage immunomodulation has been well‐established. However, it remains unclear whether K+ channels are involved in the lipid uptake of macrophages. The expression and function of the inward rectifier potassium channel (Kir2.1, KCNJ2) in Human acute monocytic leukemia cell line (THP‐1) cells and human monocytes derived macrophages (HMDMs) were investigated using RT‐PCR and western blotting, and patch clamp technique. The expression of scavenger receptors in THP‐1–derived macrophages was detected using western blotting. Expressions of Kir2.1 mRNA and protein in HMDMs were significantly decreased by 60% (P < 0.05) and 90% (P < 0.001) on macrophage maturation, but overexpressed by approximately 1.3 (P > 0.05) and 3.8 times (P = 0.001) after foam cell formation respectively. Concurrently, the Kir2.1 peak current density in HMDMs, mature macrophages and foam cells, measured at −150 mV, were −22.61 ± 2.1 pA/pF, −7.88 ± 0.60 pA/pF and −13.39 ± 0.80 pA/pF respectively (P < 0.05). In association with an up‐regulation of Kir2.1 in foam cells, the SR‐A protein level was significantly increased by over 1.5 times compared with macrophages (P < 0.05). THP‐1 cells contained much less lipids upon Kir2.1 knockdown and cholesterol ester/total cholesterol ratio was 29.46 ± 2.01% (P < 0.05), and the SR‐BI protein level was increased by over 6.2 times, compared to that of macrophages (P < 0.001). Kir2.1 may participate in macrophage maturation and differentiation, and play a key role in lipid uptake and foam cell formation through modulating the expression of scavenger receptors. John Wiley and Sons Inc. 2015-12-22 2016-03 /pmc/articles/PMC4759473/ /pubmed/26689595 http://dx.doi.org/10.1111/jcmm.12705 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhang, Wei
Lei, Xin‐Jun
Wang, Yi‐Fan
Wang, Dong‐Qi
Yuan, Zu‐Yi
spellingShingle Zhang, Wei
Lei, Xin‐Jun
Wang, Yi‐Fan
Wang, Dong‐Qi
Yuan, Zu‐Yi
Role of Kir2.1 in human monocyte‐derived foam cell maturation
author_facet Zhang, Wei
Lei, Xin‐Jun
Wang, Yi‐Fan
Wang, Dong‐Qi
Yuan, Zu‐Yi
author_sort Zhang, Wei
title Role of Kir2.1 in human monocyte‐derived foam cell maturation
title_short Role of Kir2.1 in human monocyte‐derived foam cell maturation
title_full Role of Kir2.1 in human monocyte‐derived foam cell maturation
title_fullStr Role of Kir2.1 in human monocyte‐derived foam cell maturation
title_full_unstemmed Role of Kir2.1 in human monocyte‐derived foam cell maturation
title_sort role of kir2.1 in human monocyte‐derived foam cell maturation
description The role of K+ channels in macrophage immunomodulation has been well‐established. However, it remains unclear whether K+ channels are involved in the lipid uptake of macrophages. The expression and function of the inward rectifier potassium channel (Kir2.1, KCNJ2) in Human acute monocytic leukemia cell line (THP‐1) cells and human monocytes derived macrophages (HMDMs) were investigated using RT‐PCR and western blotting, and patch clamp technique. The expression of scavenger receptors in THP‐1–derived macrophages was detected using western blotting. Expressions of Kir2.1 mRNA and protein in HMDMs were significantly decreased by 60% (P < 0.05) and 90% (P < 0.001) on macrophage maturation, but overexpressed by approximately 1.3 (P > 0.05) and 3.8 times (P = 0.001) after foam cell formation respectively. Concurrently, the Kir2.1 peak current density in HMDMs, mature macrophages and foam cells, measured at −150 mV, were −22.61 ± 2.1 pA/pF, −7.88 ± 0.60 pA/pF and −13.39 ± 0.80 pA/pF respectively (P < 0.05). In association with an up‐regulation of Kir2.1 in foam cells, the SR‐A protein level was significantly increased by over 1.5 times compared with macrophages (P < 0.05). THP‐1 cells contained much less lipids upon Kir2.1 knockdown and cholesterol ester/total cholesterol ratio was 29.46 ± 2.01% (P < 0.05), and the SR‐BI protein level was increased by over 6.2 times, compared to that of macrophages (P < 0.001). Kir2.1 may participate in macrophage maturation and differentiation, and play a key role in lipid uptake and foam cell formation through modulating the expression of scavenger receptors.
publisher John Wiley and Sons Inc.
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759473/
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