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[PMID]: 29523916
[Au] Autor:Li X; Tang Y; Ma B; Wang Z; Jiang J; Hou S; Wang S; Zhang J; Deng M; Duan Z; Tang X; Chen AF; Jiang L
[Ad] Address:Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
[Ti] Title:The peptide lycosin-I attenuates TNF-α-induced inflammation in human umbilical vein endothelial cells via IκB/NF-κB signaling pathway.
[So] Source:Inflamm Res;, 2018 Mar 10.
[Is] ISSN:1420-908X
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:OBJECTIVE: The peptide lycosin-I has anti-bacterial and anti-cancer capacities. However, the anti-inflammatory activity of lycosin-I remains unknown. We investigated whether lycosin-I could attenuate inflammation. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with lycosin-I before exposure to tumor necrosis factor-α (TNF-α). The expression of intercellular cell adhesion molecule-1 (ICAM-1), nuclear transcription factor-kappa B (NF-κB) p65 and inhibitory subunit of NF-κB alpha (IκBα) was evaluated by western blot. The expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) was detected by quantitative RT-PCR or ELISA. Immunofluorescence analysis was used to determine the impact of lycosin-I on NF-κB pathway. C57BL/6 mice were pretreated with lycosin-I before exposure with lipopolysaccharide (LPS). RESULTS: Lycosin-I significantly reduced the TNF-α-enhanced expression of IL-6, IL-8 and ICAM-1. Lycosin-I also inhibited the human monocyte cells adhesion to HUVECs. We further demonstrated that lycosin-I could effectively suppress the reaction of endothelial cells to TNF-α by inhibiting IκBα degradation. Subsequently, the phosphorylation and translocation of NF-κB p65 could also be attenuated. Furthermore, lycosin-I exhibited a significant protection of C57BL/6 mice against LPS-induced death. CONCLUSIONS: Our results suggested that the anti-inflammatory activity of lycosin-I was associated with NF-κB activation and lycosin-I had potential to be a novel therapeutic candidate for inflammatory diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher
[do] DOI:10.1007/s00011-018-1138-7

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[PMID]: 28467723
[Au] Autor:Diaz-Morales N; Rovira-Llopis S; Bañuls C; Lopez-Domenech S; Escribano-Lopez I; Veses S; Jover A; Rocha M; Hernandez-Mijares A; Victor VM
[Ad] Address:1 Service of Endocrinology and Nutrition, University Hospital Doctor Peset , Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain .
[Ti] Title:Does Metformin Protect Diabetic Patients from Oxidative Stress and Leukocyte-Endothelium Interactions?
[So] Source:Antioxid Redox Signal;27(17):1439-1445, 2017 Dec 10.
[Is] ISSN:1557-7716
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Since metformin can exert beneficial vascular effects, we aimed at studying its effect on reactive oxygen species (ROS) production, antioxidant enzyme expression, levels of adhesion molecules, and leukocyte-endothelium interactions in the leukocytes from type 2 diabetic (T2D) patients. The study was carried out in 72 T2D patients (41 of whom were treated with metformin for at least 12 months at a dose of 1700 mg per day), and in 40 sex- and age-matched control subjects. Leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, whereas metformin was shown to revert these effects. No changes were observed on total ROS production and the expression levels of superoxide dismutase 1 and catalase. Furthermore, increases in leukocyte-endothelial interactions and intercellular adhesion molecule-1 and P-selectin levels were found in T2D and were also restored in metformin-treated patients. Our findings raise the question of whether metformin could modulate the appearance of atherosclerosis in T2D patients and reduce vascular events by decreasing leukocyte oxidative stress through an increase in gpx1 and sirt3 expression, and undermining adhesion molecule levels and leukocyte-endothelium interactions. Antioxid. Redox Signal. 27, 1439-1445.
[Mh] MeSH terms primary: Diabetes Mellitus, Type 2/drug therapy
Endothelial Cells/drug effects
Hypoglycemic Agents/administration & dosage
Leukocytes/drug effects
Metformin/administration & dosage
Oxidative Stress/drug effects
[Mh] MeSH terms secundary: Aged
Catalase
Cell Adhesion
Diabetes Mellitus, Type 2/genetics
Diabetes Mellitus, Type 2/metabolism
Endothelial Cells/metabolism
Female
Glutathione Peroxidase/genetics
Humans
Hypoglycemic Agents/pharmacology
Intercellular Adhesion Molecule-1/metabolism
Leukocytes/metabolism
Male
Metformin/pharmacology
Middle Aged
P-Selectin/metabolism
Reactive Oxygen Species/metabolism
Sirtuin 3/genetics
Superoxide Dismutase-1/genetics
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Hypoglycemic Agents); 0 (ICAM1 protein, human); 0 (P-Selectin); 0 (Reactive Oxygen Species); 0 (SOD1 protein, human); 126547-89-5 (Intercellular Adhesion Molecule-1); 9100L32L2N (Metformin); EC 1.11.1.- (glutathione peroxidase GPX1); EC 1.11.1.6 (Catalase); EC 1.11.1.9 (Glutathione Peroxidase); EC 1.15.1.1 (Superoxide Dismutase-1); EC 3.5.1.- (SIRT3 protein, human); EC 3.5.1.- (Sirtuin 3)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:170504
[St] Status:MEDLINE
[do] DOI:10.1089/ars.2017.7122

  3 / 21744 MEDLINE  
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[PMID]: 29518395
[Au] Autor:Huang W; Huang M; Ouyang H; Peng J; Liang J
[Ad] Address:Department of the first Orthopedics,the 2nd Affiliated Hospital, Guiyang College of Traditional Chinese Medicine,Guiyang, Guizhou, China. Electronic address: huangweichen1573@sina.com.
[Ti] Title:Oridonin inhibits vascular inflammation by blocking NF-κB and MAPK activation.
[So] Source:Eur J Pharmacol;, 2018 Mar 05.
[Is] ISSN:1879-0712
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Oridonin, an active diterpenoid compound isolated from the plant Rabdosia Rrubescens, has various pharmacological activities, including antioxidant, anti-tumor capacities and anti-inflammation. In the present study, we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism. Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay. The protein expression was measured by Western blot. NF-κB p65 translocation was measured by immunofluorescence. Acute lung inflammation model was used to evaluate leukocyte infiltration in vivo. The endothelial-leukocyte adhesion and the leukocyte transmigration were profoundly reduced by oridonin. Oridonin dramatically inhibited the expression of TNF-α-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) and E-selectin) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1(MCP-1)). Oridonin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, Oridonin also suppressed the TNF-α-activated MAPK and Nuclear factor kappa B (NF-κB) activation. Our results suggest that oridonin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of MAPK and NF-κB activation, which may have a potential therapeutic use for inflammatory vascular diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher

  4 / 21744 MEDLINE  
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[PMID]: 29307595
[Au] Autor:Karthikkeyan G; Nareshkumar RN; Aberami S; Sulochana KN; Vedantham S; Coral K
[Ad] Address:R.S. Mehta Jain Department of Biochemistry and Cell Biology, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, India; School of Chemical and Biotechnology, SASTRA University, India.
[Ti] Title:Hyperglycemia induced early growth response-1 regulates vascular dysfunction in human retinal endothelial cells.
[So] Source:Microvasc Res;117:37-43, 2018 May.
[Is] ISSN:1095-9319
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Early growth response-1 (Egr-1) protein upregulation is reported in diabetes and vascular disorders. This study aims at deciphering its role in hyperglycemia induced changes of retinal endothelium. Human retinal endothelial cells (hRECs) were exposed to hyperglycemia (25mM) and normoglycemia (5.5mM). Gene silencing was done using siRNA against Egr-1. Transcript and protein level analysis of Egr-1 and gene targets were done using qPCR and immunoblotting respectively in hRECs, diabetic and nondiabetic human retina and immunofluorescence for localization in retinal sections. Hyperglycemia induced Egr-1 and vascular endothelial growth factor-A (VEGF-A) but not pigment epithelium derived factor (PEDF) in hRECs. Expression of Egr-1 repressor NGFI-A binding protein-2 (NAB-2) was unaltered. Egr-1 downstream gene targets, tissue factor (TF) and intercellular adhesion molecule-1 (ICAM-1) expression were increased in hRECs which was reduced by Egr-1 silencing in hyperglycemia. Diabetic retina, showed an increase in Egr-1, VEGF-A and gene target TF, ICAM-1 but not NAB-2 and PEDF similar to the changes seen in hyperglycemic hRECs. Hyperglycemic induction of Egr-1 and absence of NAB-2 repression in retinal endothelium, up-regulates downstream genes involved in pro-thrombotic and pro-inflammatory pathways linking Egr-1 in diabetes mediated vascular aberration of retina.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review

  5 / 21744 MEDLINE  
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[PMID]: 29517712
[Au] Autor:Yarur AJ; Jain A; Quintero MA; Czul F; Deshpande AR; Kerman DH; Abreu MT
[Ad] Address:Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI.
[Ti] Title:Inflammatory Cytokine Profile in Crohn's Disease Nonresponders to Optimal Antitumor Necrosis Factor Therapy.
[So] Source:J Clin Gastroenterol;, 2018 Mar 06.
[Is] ISSN:1539-2031
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: A significant number of patients receiving therapy with antitumor necrosis factor (TNF) agents for Crohn's disease experience primary or secondary nonresponse. The aim of this study was to assess whether patients with nonresponse to anti-TNF agents have increased expression of alternative cytokine pathways. METHODS: We designed a prospective, cross-sectional study that included patients with Crohn's disease receiving anti-TNF undergoing colonoscopy with adequate serum trough drug levels (≥8 µg/mL) and without anti-drug antibodies. Inflammatory cytokines and cell adhesions markers measured included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin (IL)-8, IL-1ß, and IL-6. The primary outcome was the presence of active endoscopic inflammation defined as the presence of at least 1 ulceration ≥5 mm. RESULTS: In total, 47 patients were included. Patients with active inflammation had significantly higher levels of ICAM-1 and IL-1ß when compared with those without intestinal inflammation (45.9 vs. 35.8 ng/mL, P<0.0001 and 3.2 vs. 1.5 pg/mL, P=0.002, respectively). There were no significant differences in the other study variables. Using receiving operating curves, ICAM and IL-1ß had a good correlation (receiver operating characteristic ≥0.8) with inflammation in this cohort of patients with "anti-TNF resistance." The results were similar in the group of patients with previous anti-TNF exposure. CONCLUSION: Our study suggests that patients who have active inflammation with seemingly adequate serum anti-TNF levels have increased levels of specific inflammatory pathways that may serve as biomarkers of nonresponse as well as potential targets of therapy in anti-TNF nonresponders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1097/MCG.0000000000001002

  6 / 21744 MEDLINE  
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[PMID]: 29515232
[Au] Autor:Itoh H; Kadomatsu T; Tanoue H; Yugami M; Miyata K; Endo M; Morinaga J; Kobayashi E; Miyamoto T; Kurahashi R; Terada K; Mizuta H; Oike Y
[Ad] Address:Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
[Ti] Title:TET2-dependent IL-6 induction mediated by the tumor microenvironment promotes tumor metastasis in osteosarcoma.
[So] Source:Oncogene;, 2018 Mar 08.
[Is] ISSN:1476-5594
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The tumor microenvironment promotes epigenetic changes in tumor cells associated with tumor aggressiveness. Here we report that in primary tumor cells, increased interleukin-6 (IL-6) expression brought on by DNA demethylation of its promoter by ten-eleven translocation 2 (TET2) promotes lung metastasis in osteosarcoma (OS). Xenograft experiments show increased IL-6 expression and decreased methylation of its promoter in OS cells after implantation relative to before implantation. In addition, changes in IL-6 methylation and expression seen in OS cells at the primary site were maintained at the metastatic site. TET2 knockdown in OS cells suppressed upregulation of IL-6 and demethylation of its promoter in xenograft tumors and decreased tumor metastasis. We also present evidence showing that tumor cell-derived IL-6 facilitates glycolytic metabolism in tumor cells by activating the MEK/ERK1/2/hypoxia-inducible transcription factor-1α (HIF-1α) pathway and increases lung colonization by OS cells by upregulating expression of intercellular adhesion molecule-1 (ICAM-1), enhancing tumor metastasis. Blocking IL-6 signaling with a humanized monoclonal antibody against the IL-6 receptor reduced lung metastasis and prolonged survival of xenografted mice. These findings suggest that TET2-dependent IL-6 induction enables acquisition of aggressive phenotypes in OS cells via the tumor microenvironment and that blocking IL-6 signaling could be serve as a potential therapy to antagonize metastasis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1038/s41388-018-0160-0

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[PMID]: 29513943
[Au] Autor:Hashmp SF; Sattar MZA; Rathore HA; Ahmadi A; Johns EJ
[Ti] Title:A CRITICAL REVIEW ON PHARMACOLOGICAL SIGNIFICANCE OF HYDROGEN SULFIDE (H2S) ON NF-κB CONCENTRATION AND ICAM-1 EXPRESSION IN RENAL ISCHEMIA REPERFUSION INJURY.
[So] Source:Acta Pol Pharm;74(3):747-752, 2017 May.
[Is] ISSN:0001-6837
[Cp] Country of publication:Poland
[La] Language:eng
[Ab] Abstract:Until recently hydrogen sulfide (H2S) was the least appreciated of the three gasotransmitters but now recognized as 3Y gaseous mediator after nitric oxide(NO) and carbon monoxide (CO). H2S regulates a number of physiological processes like vasorelaxation, prevention of inflammation, leukocyte adhesion, anti-prolifera- tive effects, anti-thrombotic effects, resistance to oxidative stress and protection against ischemia reperfusion injury (IRI). However, considerable amount of research is still needed to evaluate the mechanisms involved in the therapeutic effects of H2S in IRI such as its effects on nuclear factor-kappa B (NF-KB) concentration and intercellular adhesion molecule-1 (ICAM-1) expression in renal IRI and ARF (acute renal failure). More than a decade of good repute among researchers, H2S research has certain results that need to be clarified more such as whether H2S is pro-inflammatory or anti-inflammatory agent. Moreover, pathways adopted by H2S in the protein modification and its effects on cell signalling specially its effect on NF-KB in the process of inflamma- tion are not fully elucidated. H2S has delighted researchers and a great deal of information is being generated every year.The main purpose of the review is to provide an update on the development in the research of H2S in renal IRI due to uncertainty of the exact role of H2S on ICAM-1 expression and NF-KB concentration whether it inhibits or activates them.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Process

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[PMID]: 29513760
[Au] Autor:Han J; Li Y; Liu X; Zhou T; Sun H; Edwards P; Gao H; Yu FS; Qiao X
[Ad] Address:Department of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States of America.
[Ti] Title:Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo.
[So] Source:PLoS One;13(3):e0193031, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (p<0.05). Several inflammatory molecules upregulated by tumor necrosis factor-α in human retinal vascular endothelial cells were markedly reduced by metformin, including nuclear factor kappa B p65 (NFκB p65), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8). Further, metformin significantly decreased retinal leukocyte adhesion (p<0.05) in streptozotocin-induced diabetic mice. Activation of AMP-activated protein kinase was found to play a partial role in the suppression of ICAM-1 and MCP-1 by metformin, but not in those of NFκB p65 and IL-8. Our findings support the notion that metformin has considerable anti-angiogenic and anti-inflammatory effects on retinal vasculature. Metformin could be potentially used for the purpose of treating diabetic retinopathy in addition to blood glucose control in diabetic patients.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0193031

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[PMID]: 29510400
[Au] Autor:Yang WS; Kim JJ; Lee MJ; Lee EK; Park SK
[Ad] Address:Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
[Ti] Title:ADAM17-Mediated Ectodomain Shedding of Toll-Like Receptor 4 as a Negative Feedback Regulation in Lipopolysaccharide-Activated Aortic Endothelial Cells.
[So] Source:Cell Physiol Biochem;45(5):1851-1862, 2018 Feb 28.
[Is] ISSN:1421-9778
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:BACKGROUND/AIMS: Lipopolysaccharide (LPS)-activated monocytes/macrophages develop endotoxin tolerance in part by reducing cell surface toll-like receptor 4 (TLR4) through cluster of differentiation 14 (CD14)-dependent endocytosis. In case of endothelial cells, CD14 is expressed in low copy numbers as compared with monocytes/macrophages. Thus, we explored how endothelial cells regulate TLR4 expression after LPS stimulation. METHODS: Cultured human aortic endothelial cells (HAECs) were treated with LPS. TLR4 expression was analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorescent substrate. RESULTS: TLR4 in cell lysate began to decrease within 30 min of LPS treatment with a maximal reduction at 2 h, and it was accompanied by an increase of N-terminal fragment of TLR4 in culture supernatant, indicating ectodomain shedding of the receptor. LPS activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while LPS-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. LPS-induced ectodomain shedding of TLR4 was attenuated by siRNA depletion of ADAM17 as well as TAPI-2 (an inhibitor of ADAM family) and SB203580. LPS pretreatment resulted in a blunted response of p38 MAPK activation to further LPS stimulation. In the cells depleted of ADAM17, LPS-induced p38 MAPK activation was prolonged and LPS-induced intercellular adhesion molecule-1 expression was potentiated. CONCLUSION: HAECs respond to LPS by rapid shedding of the ectodomain of TLR4 and thereby reduce the responsiveness to subsequent LPS exposure. ADAM17, downstream of p38 MAPK, is implicated in the ectodomain cleavage of TLR4.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher
[do] DOI:10.1159/000487876

  10 / 21744 MEDLINE  
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[PMID]: 29371247
[Au] Autor:Li X; Shao Y; Sha X; Fang P; Kuo YM; Andrews AJ; Li Y; Yang WY; Maddaloni M; Pascual DW; Luo JJ; Jiang X; Wang H; Yang X
[Ad] Address:From the Centers for Metabolic Disease Research, Cardiovascular Research, and Thrombosis Research (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), Department of Pharmacology (X.L., Y.S., X.S., P.F., Y.L., W.Y.Y., X.J., H.W., X.Y.), and Department of Neurology (J.J.L.), Temple University Lew
[Ti] Title:IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14 (Histone 3 Lysine 14).
[So] Source:Arterioscler Thromb Vasc Biol;38(3):599-609, 2018 Mar.
[Is] ISSN:1524-4636
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: IL-35 (interleukin-35) is an anti-inflammatory cytokine, which inhibits immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. It remains unknown whether atherogenic stimuli induce IL-35 and whether IL-35 inhibits atherogenic lipid-induced endothelial cell (EC) activation and atherosclerosis. EC activation induced by hyperlipidemia stimuli, including lysophosphatidylcholine is considered as an initiation step for monocyte recruitment and atherosclerosis. In this study, we examined the expression of IL-35 during early atherosclerosis and the roles and mechanisms of IL-35 in suppressing lysophosphatidylcholine-induced EC activation. APPROACH AND RESULTS: Using microarray and ELISA, we found that IL-35 and its receptor are significantly induced during early atherosclerosis in the aortas and plasma of ApoE (apolipoprotein E) knockout mice-an atherosclerotic mouse model-and in the plasma of hypercholesterolemic patients. In addition, we found that IL-35 suppresses lysophosphatidylcholine-induced monocyte adhesion to human aortic ECs. Furthermore, our RNA-sequencing analysis shows that IL-35 selectively inhibits lysophosphatidylcholine-induced EC activation-related genes, such as ICAM-1 (intercellular adhesion molecule-1). Mechanistically, using flow cytometry, mass spectrometry, electron spin resonance analyses, and chromatin immunoprecipitation-sequencing analyses, we found that IL-35 blocks lysophosphatidylcholine-induced mitochondrial reactive oxygen species, which are required for the induction of site-specific H3K14 (histone 3 lysine 14) acetylation, increased binding of proinflammatory transcription factor AP-1 in the promoter of ICAM-1, and induction of ICAM-1 transcription in human aortic EC. Finally, IL-35 cytokine therapy suppresses atherosclerotic lesion development in ApoE knockout mice. CONCLUSIONS: IL-35 is induced during atherosclerosis development and inhibits mitochondrial reactive oxygen species-H3K14 acetylation-AP-1-mediated EC activation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Data-Review
[do] DOI:10.1161/ATVBAHA.117.310626


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