IL-33 Reduces Macrophage Foam Cell Formation

McLaren, James E.; Michael, Daryn Robert; Salter, Rebecca Claire; Ashlin, Timothy Gordon; Calder, Claudia J.; Miller, Ashley M.; Liew, Foo Y.; Ramji, Dipak Purshottam

doi:10.4049/jimmunol.1000520

Cited by 163 publications

(194 citation statements)

References 39 publications

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“…Additionally, experiments were performed in both THP-1 macrophages and primary cultures of HMDMs to rule out the possibility that the results obtained in this study are peculair to the THP-1 cell line. Similar to THP-1 macrophages, HMDMs have been used extensively to study foam cell formation (8,19,23,24). The specificity of knockdown was confirmed by RT-qPCR, which indicated .50% inhibition in the expression of the corresponding RNA (Fig.…”

Section: Ifn-g Activates Erk In Macrophagesmentioning

confidence: 98%

“…We therefore determined the effect of the ERK1/2 inhibitor PD98059 on the IFN-g-induced uptake of AcLDL by THP-1 macrophages. THP-1 macrophages are used extensively to study macrophage foam cell formation, including the action of IFN-g, and express all the major proteins involved in this process, including scavenger receptors (8,(19)(20)(21). Initial experiments showed that maximal AcLDL uptake occurred at 24 h, which was therefore used for all subsequent experiments.…”

Section: Ifn-g Activates Erk In Macrophagesmentioning

confidence: 99%

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ERK Is Integral to the IFN-γ–Mediated Activation of STAT1, the Expression of Key Genes Implicated in Atherosclerosis, and the Uptake of Modified Lipoproteins by Human Macrophages

McLaren

Michael

et al. 2010

The Journal of Immunology

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The proinflammatory cytokine IFN-γ is a master regulator of atherosclerosis and mediates its cellular actions mainly through STAT1. Unfortunately, the impact of other IFN-γ inducible pathways on STAT1 activation and the regulation of downstream responses associated with atherosclerosis in human macrophages are poorly understood and were therefore investigated. In this study, we demonstrate that the IFN-γ–mediated phosphorylation of STAT1 on Ser727, crucial for its maximal activity, was attenuated in human macrophages by pharmacological inhibition of ERK. In these cells, IFN-γ induced changes in the expression of several key genes implicated in atherosclerosis, such as MCP-1, through an ERK-dependent mechanism. Additionally, the IFN-γ–induced activity of STAT1-responsive promoters was attenuated by transfection of dominant-negative forms of ERK and other key components of this pathway. Furthermore, the IFN-γ–induced uptake of acetylated and oxidized low-density lipoprotein by human macrophages was attenuated by pharmacological inhibition or RNA interference–mediated knockdown of ERK. These studies suggest a critical role for ERK signaling in the IFN-γ–mediated changes in macrophage cholesterol homeostasis and gene expression during atherosclerosis.

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Section: Ifn-g Activates Erk In Macrophagesmentioning

confidence: 98%

Section: Ifn-g Activates Erk In Macrophagesmentioning

confidence: 99%

ERK Is Integral to the IFN-γ–Mediated Activation of STAT1, the Expression of Key Genes Implicated in Atherosclerosis, and the Uptake of Modified Lipoproteins by Human Macrophages

McLaren

Michael

et al. 2010

The Journal of Immunology

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“…Thus, our data collectively indicate that downregulation of miR-487b is strongly linked to the increased production of IL-33 and the induction of a proinflammatory status of macrophages. Currently, there are a few studies showing that IL-33 or miRNAs participate in the regulation of the differentiation and function of macrophages (5,6,8,38). To our knowledge, our study is the first to demonstrate that miR-487b acts as a negative regulator of macrophage activation by targeting IL-33.…”

Section: Discussionmentioning

confidence: 63%

“…Activation of ST2 by IL-33 induces the production of a range of proinflammatory cytokines and chemokines from these immune cells. In particular, IL-33 was shown to regulate macrophage foam cell formation, promote the polarization of alternatively activated macrophages, and enhance macrophage-regulated antibacterial immunity (4)(5)(6). Furthermore, Dyer et al (7) recently showed that IL-33 acts in concert with SCF, Flt3L, and M-CSF to regulate macrophage differentiation.…”

mentioning

confidence: 99%

MicroRNA-487b Is a Negative Regulator of Macrophage Activation by Targeting IL-33 Production

Xiang

Eyers

Herbert

et al. 2016

The Journal of Immunology

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MicroRNAs (miRNAs) are short noncoding RNAs that regulate a broad spectrum of biological processes, including immune responses. Although the contributions of miRNAs to the function of immune cells are beginning to emerge, their specific roles remain largely unknown. IL-33 plays an important role in macrophage activation for innate host defense and proinflammatory responses. In this study, we report that miR-487b can suppress the levels of mRNA and protein for IL-33 during the differentiation of bone marrow–derived macrophages (BMDMs). This results in inhibition of IL-33–induced expression of Ag-presenting and costimulatory molecules and proinflammatory mediators. A luciferase assay showed that miR-487b binds to the IL-33 3′-untranslated region. We also confirmed that IL-33 directly promotes the activation of BMDMs by increasing the expression of MHC class I, MHC class II, CD80/CD86, and inducible NO synthase (iNOS) in a dose-dependent manner. Exposure of BMDMs to the TLR4 ligand, LPS, decreased miR-487b expression, increased IL-33 transcript levels, and induced the production of proinflammatory mediators (e.g., iNOS, IL-1β, IL-6, and TNF-α). Treatment with a specific inhibitor of miR-487b function also resulted in increased levels of IL-33 mRNA, which augmented LPS-induced expression of these inflammatory mediators in macrophages. Collectively, our results indicate that miR-487b plays a negative regulatory role in macrophages by controlling the levels of IL-33 transcript and protein to fine-tune innate immune host defense and proinflammatory responses of these cells. Thus, miR-487b plays an important role in the regulation of macrophage homeostasis and activation by targeting IL-33 transcripts.

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“…и со-авт. [28] показали, что IL-33 оказывает защитные эффекты при атеросклерозе, главным образом за счет уменьшения образования макрофагов, которые являются ключевой особенностью ате-росклеротических бляшек. В различных экспе-риментах было показано, что IL-33 через свой рецептор может ингибировать экспрессию де-зинтегрина, металлопротеиназы 1, 4, 5 и тромбо-спондина, которые могут играть роль в регуляции устойчивости атеросклеротической бляшки [2].…”

Section: Il-33 и атеросклерозunclassified

Interleukin 33 and Fibrosis: Pathogenesis Updated

Геннадьевна¹,

Груздева²,

Dyleva³

et al. 2018

Med. immunol.

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Адрес для переписки:Учасова Евгения Геннадьевна ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний» 650002, Россия, г. Кемерово, Сосновый бульвар, 6. Тел.: 8 (3842) 64-05-53. Е-mail: evg.uchasova@yandex.ru Diseases 650002, Russian Federation, Kemerovo, Sosnovy bvld, Образец цитирования: Е.Г. Учасова, О.В. Груздева, Ю.А. Дылева, В.Н. Каретникова «Интерлейкин-33 и фиброз: современный взгляд на патогенез» // Медицинская иммунология, 2018. Т. 20, № 4. С. 477-484. doi: 10.15789/1563-0625-2018-4-477-484 © Учасова Е.Г. и соавт., 2018 For citation: E.G. Uchasova, O.V. Gruzdeva, Yu.A. Dileva, V.N. Karetnikova "Interleukin 33 and fibrosis: pathogenesis updated", Medical Immunology (Russia) /Meditsinskaya Immunologiya, 2018, Vol. 20, no. 4, pp. 477-484. doi: 10.15789/1563-0625-2018-4-477-484 DOI: 10.15789/1563-0625-2018 Резюме. Интерлейкин-33 (IL-33) член семейства IL-1, который широко экспрессируется во всех типах клеток. IL-33 был идентифицирован как функциональный лиганд для рецепторного комплек-са плазматической мембраны, который представляет собой гетеродимер, состоящий из связанного с мембраной рецептора ST2 (стимулирующий фактор роста). IL-33 участвует в развитии иммунно-го ответа с преимущественным высвобождением провоспалительных цитокинов Т-хелперов 2 типа. IL-33 широко экспрессируется в различных структурных клетках, таких как эпителиальные, эндоте-лиальные и клетки гладкой мускулатуры. Во время некроза из этих клеток (после повреждения тка-ни или повреждения клеток) экспрессия IL-33 увеличивается, и он высвобождается во внеклеточное пространство и действует как сигнал эндогенной опасности, отправляя предупреждающие сигналы на соседние клетки и ткани. В последнее время появилось много исследований, в которых показано, что IL-33 может участвовать в механизме развития и прогрессирования фиброза различных органов, но при этом оказывает противовоспалительное действие на механизмы развития других заболеваний. В данном обзоре будут обсуждаться биологические характеристики IL-33 и роль сигнального пути IL-33/ST2 в развитии фиброза. Abstract. Interleukin 33 (IL-33) is a member of the IL-1 family, which is widely expressed on all types of cells. IL-33 was identified as a functional ligand for the plasma membrane receptor complex, which is a heterodimer consisting of a membrane bound ST2 receptor (growth stimulating factor). IL-33 is involved in the development of immune response with predominant release of pro-inflammatory T helper type 2 cytokines. IL-33 is widely expressed on various structure-forming cells, such as epithelial, endothelial and smooth muscle cells. Increased expression of IL-33 is observed during necrosis of these cells (after tissue or cell damage), and it is released into extracellular space, and acts as an endogenous danger signal, sending a sort of warnings to neighboring cells and tissues. Recently, many studies have shown that IL-33 can participate in development and progression of fibrosis in various organs. However, it exerts ant...

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IL-33 Reduces Macrophage Foam Cell Formation

Abstract: Material

Cited by 163 publications

References 39 publications

ERK Is Integral to the IFN-γ–Mediated Activation of STAT1, the Expression of Key Genes Implicated in Atherosclerosis, and the Uptake of Modified Lipoproteins by Human Macrophages

ERK Is Integral to the IFN-γ–Mediated Activation of STAT1, the Expression of Key Genes Implicated in Atherosclerosis, and the Uptake of Modified Lipoproteins by Human Macrophages

MicroRNA-487b Is a Negative Regulator of Macrophage Activation by Targeting IL-33 Production

Interleukin 33 and Fibrosis: Pathogenesis Updated

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