Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-<i>κ</i>B Pathway

Jin, Xian; Yao, Tongqing; Zhou, Zhong’e; Zhu, Jian; Zhang, Song; Hu, Wei; Shen, Chengxing

doi:10.1155/2015/732450

Cited by 151 publications

(127 citation statements)

References 40 publications

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“…Synthetic ALE could increase the expression of IL-6, IL-8, MCP-1, and iNOS in induced THP-1 monocytes32. Furthermore, AGEs enhanced BMDM cells polarization into M1 macrophage with producing IL-6 and TNF-a proinflammatory cytokines and upregulating the expressions of CD11c and CD86 through activating RAGE/NF-κB pathway in mice33. In addition, AGEs has been shown to induce autophagy in some cells, such as hepatic stellate cells34, cardimyocytes35, vascular smooth muscle cells36, and endothelial cells37.…”

Section: Discussionmentioning

confidence: 92%

AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

Guo

Cai

et al. 2016

Sci Rep

105

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Autophagy is essential in physiological and pathological processes, however, the role of autophagy in cutaneous wound healing and the underlying molecular mechanism remain elusive. We hypothesized that autophagy plays an important role in regulating wound healing. Here, we show that enhanced autophagy negatively impacts on normal cutaneous healing process and is related to chronic wounds as demonstrated by the increased LC3 in diabetic mice skin or patients’ chronic wounds. In addition, inhibition of autophagy by 3-MA restores delayed healing in C57BL/6 or db/db mice, demonstrating that autophagy is involved in regulating wound healing. Furthermore, we identify that macrophage is a major cell type underwent autophagy in wounds and increased autophagy induces macrophages polarization into M1 with elevated CD11c population and gene expressions of proinflammatory cytokines. To explore the mechanism underlying autophagy-impaired wound healing, we tested the role of IRF8, a regulator of autophagy, in autophagy-modulated macrophages polarization. IRF8 activation is up-regulating autophagy and M1 polarization of macrophages after AGEs (advanced glycation endproducts) treatment, blocking the IRF8 with shIRF8 inhibits autophagic activity and M1 polarization. In summary, this study elucidates that AGEs induces autophagy and modulates macrophage polarization to M1 via IRF8 activation in impairment of cutaneous wound healing.

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Section: Discussionmentioning

confidence: 92%

AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

Guo

Cai

et al. 2016

Sci Rep

105

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“…In its turn, protein kinase C is responsible for the activation of NF-kB [17] contributing to improvements in adhesion of monocytes to the vascular wall [17,18] . Jin et al [19] found that AGEs not only predominantly induce macrophages to secrete inflammatory cytokines, but also induce M1 polarization. Moreover, AGEs activate the RAGE/NF-kB pathway, whereas the blockade of RAGE or NF-kB can attenuate macrophage activation [19,20] .…”

Section: Discussionmentioning

confidence: 99%

“…Jin et al [19] found that AGEs not only predominantly induce macrophages to secrete inflammatory cytokines, but also induce M1 polarization. Moreover, AGEs activate the RAGE/NF-kB pathway, whereas the blockade of RAGE or NF-kB can attenuate macrophage activation [19,20] . We also found a direct correlation between the levels of HbA1c and TNF-α in patients with newly diagnosed diabetes [ Figure 1].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease

Nikiforov¹,

Galstyan²,

Недосугова³

et al. 2017

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How to cite this article: Nikiforov NG, Galstyan KO, Nedosugova LV, Elizova NV, Kolmychkova KI, Ivanova EA. Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease. Vessel Plus 2017;1:192-5.Aim: Type 2 diabetes mellitus (T2DM) is associated with rapid progression of atherosclerosis. There is no doubt that inflammation is involved in atherogenesis. Recent studies showed the relationship between the development of atherosclerotic plaque formation and the amount of pro-inflammatory (M1) activated macrophages in situ. Methods: The authors studied the ability of circulating monocytes isolated from patients with diabetes (n = 28), coronary heart disease (CHD) (n = 27) and healthy subjects (n = 50) to be activated into M1 phenotype in vitro. Results: Increased levels of basal and stimulated secretion of tumor necrosis factor alpha (TNF-α) was observed in diabetic patients compared with healthy subjects. On the contrary, in patients with CHD, decreased secretion of the pro-inflammatory cytokine, TNF-α, was found. A direct correlation between glycated hemoglobin (HbA1c) levels in T2DM patients and basal secretion of TNF-α from monocytes was observed. Conclusion: The authors found diametrically different responses of monocytes from T2DM and CHD under pro-inflammatory stimuli. Key words:Type 2 diabetes mellitus, coronary heart disease, M1/M2 monocyte polarization, oxidative stress, atherosclerosis, inflammatory ABSTRACTArticle history:

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“…Именно ПКС ответ ственна за активиза-цию NFκB способствующего повышению адгезии моноцитов к сосудистой стенке и их дифференци-ровке в макрофаги. Вместе с тем, образующиеся в условиях гипергликемии конечные продукты нефер-ментного гликирования (КПНГ), подавляют противо-воспалительную активность ядерных рецепторов PPARɣ [13], что доказывается выраженным противо-воспалительным эффектом агонистов PPARɣ [14].…”

Section: результатыunclassified

Significance of M1 and M2 Polarization of Monocytes-Macrophages in the Blood for Atherosclerosis Risk Assessment in Type 2 Diabetes Comparing With Coronary Heart Disease

Галстян¹,

Недосугова²,

Nikiforov³

et al. 2017

Russ J Cardiol

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Цель. Определение фенотипов провоспалительной (М1) и противовоспали-тельной (М2) активации моноцитов крови у больных сахарным диабетом 2 типа (СД 2) в сравнении с пациентами с ишемической болезнью сердца (ИБС). Материал и методы. Обследовано 55 пациентов с ИБС, из которых у 28 паци-ентов (11м/17ж) при поступлении в клинику впервые был выявлен СД 2, (уро-вень HbA 1c 9,7%, SD=2,4), ранее не получавших сахароснижающую терапию, и 27 больных с ИБС (20м/7ж), без нарушений углеводного обмена. В качестве контроля обследовано 50 здоровых лиц без нарушений углеводного и липид-ного обмена. Методом иммуноферментного анализа (ИФА) определяли про-воспалительную активацию моноцитов по спонтанной и индуцированной интерфероном гамма (ИФН-ɣ) секреции провоспалительного цитокина фак-тора некроза опухоли альфа (ФНО-α), и противовоспалительную активацию моноцитов по спонтанной и индуцированной интерлейкином-4 (ИЛ-4) секре-ции противовоспалительного цитокина CCL18. Результаты. Выявлена повышенная способность моноцитов крови больных СД 2 к секреции как провоспалительного, так и противовоспалительного цито-кинов в сравнении с контролем и пациентами с ИБС. Базальная секреция ФНО-α была выше контрольного уровня в 2,8 раз, стимулированная секреция была выше в 2,2 раза. Показатели базальной и стимулированной секреции ФНО-α у пациентов с ИБС были достоверно ниже контроля. Выявлена положи-тельная корреляция между уровнем HbA 1c и базальной секрецией ФНО-α. Базальная и стимулированная секреция противовоспалительного цитокина CCL18 у пациентов с СД 2 была достоверно выше контрольного уровня и составила 28 пг/мл (SD=3) и 1158 (SD=68) пг/мл культуральной среды, соот-ветственно, а у пациентов с ИБС эти показатели были ниже контрольного уровня и составили 0,26 пг/мл (SD=0,14) и 65 (SD=33) пг/мл, соответственно. Заключение. При СД 2 отмечается дисбаланс М1/M2 активации моноцитов по сравнению с контролем и ИБС, что указывает на избыточную активацию по провоспалительному фенотипу. Aim. To assess the phenotypes of proinflammatory (M1) and anti-inflammatory (M2) activation of blood monocytes in type 2 diabetes (DM2) comparing to coronary heart disease patients (CHD). Material and methods. Totally, 55 CHD patients assessed, of those 28 (11M/17F) were first time diagnosed with DM2 at current hospitalization (HbA 1c level 9,7% SD=2,4), not taking previously any glucose lowering therapy; and 27 patients with CHD (20M, 7F), with no glucose metabolism disorders. By immune enzyme assay method (IEA) proinflammatory monocyte activation was evaluated by spontaneous and interferon gamma (IFN-ɣ) induced secretion of proinflammatory cytokine tumour necrosis factor alpha (TNF-α), and anti-inflammatory activation of monocytes by spontaneous and interleukin-4 (IL-4) induced secretion of antiinflammatory cytokine CCL18. SIGNIFICANCE OF M1 AND M2 POLARIZATION OF MONOCYTES-MACROPHAGES IN THE BLOOD FOR ATHEROSCLEROSIS RISK ASSESSMENT IN TYPE 2 DIABETES COMPARING WITH CORONARY HEART DISEASEResults. There was found an increased ability of monocytes in DM2 patients to secre...

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Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

Cited by 151 publications

References 40 publications

AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease

Significance of M1 and M2 Polarization of Monocytes-Macrophages in the Blood for Atherosclerosis Risk Assessment in Type 2 Diabetes Comparing With Coronary Heart Disease

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