Publications by authors named "Sae Bom Lee"

15 Publications

  • Page 1 of 1

CD28 Costimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function.

Cancer Immunol Res 2021 01 13;9(1):62-74. Epub 2020 Nov 13.

Department of Blood and Marrow Transplant and Cellular Immunotherapy, Division of Clinical Science, H. Lee Moffitt Cancer Center, Tampa, Florida.

An obstacle to the development of chimeric antigen receptor (CAR) T cells is the limited understanding of CAR T-cell biology and the mechanisms behind their antitumor activity. We and others have shown that CARs with a CD28 costimulatory domain drive high T-cell activation, which leads to exhaustion and shortened persistence. This work led us to hypothesize that by incorporating null mutations of CD28 subdomains (YMNM, PRRP, or PYAP), we could optimize CAR T-cell costimulation and enhance function. , we found that mice given CAR T cells with only a PYAP CD28 endodomain had a significant survival advantage, with 100% of mice alive after 62 days compared with 50% for mice with an unmutated endodomain. We observed that mutant CAR T cells remained more sensitive to antigen after antigen and PD-L1 stimulation, as demonstrated by increased cytokine production. The mutant CAR T cells also had a reduction of exhaustion-related transcription factors and genes such as , and Our results demonstrated that CAR T cells with a mutant CD28 endodomain have better survival and function. This work allows for the development of enhanced CAR T-cell therapies by optimizing CAR T-cell costimulation.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864379PMC
January 2021

Reciprocal change in Glucose metabolism of Cancer and Immune Cells mediated by different Glucose Transporters predicts Immunotherapy response.

Theranostics 2020 25;10(21):9579-9590. Epub 2020 Jul 25.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Republic of Korea.

The metabolic properties of tumor microenvironment (TME) are dynamically dysregulated to achieve immune escape and promote cancer cell survival. However, properties of glucose metabolism in cancer and immune cells are poorly understood and their clinical application to development of a biomarker reflecting immune functionality is still lacking. We analyzed RNA-seq and fluorodeoxyglucose (FDG) positron emission tomography profiles of 63 lung squamous cell carcinoma (LUSC) specimens to correlate FDG uptake, expression of glucose transporters (GLUT) by RNA-seq and immune cell enrichment score (ImmuneScore). Single cell RNA-seq analysis in five lung cancer specimens was performed. We tested the GLUT3/GLUT1 ratio, the GLUT-ratio, as a surrogate representing immune metabolic functionality by investigating the association with immunotherapy response in two melanoma cohorts. ImmuneScore showed a negative correlation with GLUT1 ( = -0.70, < 0.01) and a positive correlation with GLUT3 ( = 0.39, < 0.01) in LUSC. Single-cell RNA-seq showed GLUT1 and GLUT3 were mostly expressed in cancer and immune cells, respectively. In immune-poor LUSC, FDG uptake was positively correlated with GLUT1 ( = 0.27, = 0.04) and negatively correlated with ImmuneScore ( = -0.28, = 0.04). In immune-rich LUSC, FDG uptake was positively correlated with both GLUT3 ( = 0.78, = 0.01) and ImmuneScore ( = 0.58, = 0.10). The GLUT-ratio was higher in anti-PD1 responders than nonresponders ( = 0.08 for baseline; = 0.02 for on-treatment) and associated with a progression-free survival in melanoma patients who treated with anti-CTLA4 ( = 0.04). Competitive uptake of glucose by cancer and immune cells in TME could be mediated by differential GLUT expression in these cells.
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http://dx.doi.org/10.7150/thno.48954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449929PMC
June 2021

Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel.

Clin Cancer Res 2020 09 15;26(18):4823-4831. Epub 2020 Jul 15.

Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Purpose: One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).

Experimental Design: Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.

Results: We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.

Conclusions: These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501265PMC
September 2020

Gasless Total Laparoscopic Hysterectomy with New Abdominal-Wall Retraction System.

JSLS 2020 Jan-Mar;24(1)

Department of Obstetrics and Gynecology, Catholic Kwandong University, International Saint Mary's Hospital.

Background And Objectives: Gasless laparoscopy is an alternative method to reduce the number of carbon dioxide (CO)-insufflated, pneumoperitoneum-related problems including shoulder pain, postoperative nausea/vomiting, and decreased cardiopulmonary function. In this study, we investigated the feasibility of gasless total laparoscopic hysterectomy (TLH) with a newly developed abdominal-wall retraction system.

Methods: Abdominal-wall retraction for gasless laparoscopy was performed using the newly developed J-shape retractor and the Thompson surgical retractor. Surgical outcomes between gasless TLH and conventional CO-based TLH were compared for each of 40 patients for the period from January 2017 to October 2019.

Results: Between gasless TLH and conventional CO-based TLH, no significant differences were observed for age, body mass index, parity, or surgical indications. The mean retraction setup time from skin incision was 7.4 min (range: 4-12 min) with gasless TLH. The mean total operation times were 87.9 min (range: 65-170) with gasless TLH and 90 min (range: 45-180) with conventional TLH, which showed no significant difference. Estimated blood loss and uterus weight also showed no significant intergroup difference. No major complications related to the ureter, bladder, or bowel were encountered.

Conclusion: Our new abdominal-wall retraction system for gasless TLH allowed for easy setup and a proper operation field in the performance of laparoscopic hysterectomy.
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http://dx.doi.org/10.4293/JSLS.2019.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056266PMC
September 2020

Spheroid-Induced Epithelial-Mesenchymal Transition Provokes Global Alterations of Breast Cancer Lipidome: A Multi-Layered Omics Analysis.

Front Oncol 2019 21;9:145. Epub 2019 Mar 21.

Department of Biochemistry, Ajou University School of Medicine, Suwon, South Korea.

Metabolic rewiring has been recognized as an important feature to the progression of cancer. However, the essential components and functions of lipid metabolic networks in breast cancer progression are not fully understood. In this study, we investigated the roles of altered lipid metabolism in the malignant phenotype of breast cancer. Using a spheroid-induced epithelial-mesenchymal transition (EMT) model, we conducted multi-layered lipidomic and transcriptomic analysis to comprehensively describe the rewiring of the breast cancer lipidome during the malignant transformation. A tremendous homeostatic disturbance of various complex lipid species including ceramide, sphingomyelin, ether-linked phosphatidylcholines, and ether-linked phosphatidylethanolamine was found in the mesenchymal state of cancer cells. Noticeably, polyunsaturated fatty acids composition in spheroid cells was significantly decreased, accordingly with the gene expression patterns observed in the transcriptomic analysis of associated regulators. For instance, the up-regulation of , and and the down-regulation of , and were found among other lipid metabolic regulators. Significantly, the ratio of C22:6n3 (docosahexaenoic acid, DHA) to C22:5n3 was dramatically reduced in spheroid cells analogously to the down-regulation of . Following mechanistic study confirmed the up-regulation of and down-regulation of , and in the spheroid cells. Furthermore, the depletion of induced metastatic characteristics in breast cancer cells via the SREBPs axis. A subsequent large-scale analysis using 51 breast cancer cell lines demonstrated the reduced expression of in basal-like phenotypes. Breast cancer patients with low expression exhibited poor prognoses (HR = 0.76, CI = 0.67-0.86). Collectively, expression is associated with the malignant phenotypes and appear to be a novel prognostic biomarker in breast cancer. In conclusion, the present study demonstrates that there is a global alteration of the lipid composition during EMT and suggests the down-regulation of induces lipid metabolism reprogramming in breast cancer and contributes to their malignant phenotypes.
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http://dx.doi.org/10.3389/fonc.2019.00145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437068PMC
March 2019

Whole Exome and Transcriptome Analyses Integrated with Microenvironmental Immune Signatures of Lung Squamous Cell Carcinoma.

Cancer Immunol Res 2018 07 2;6(7):848-859. Epub 2018 May 2.

Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea.

The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples. We used the information to predict subtype-specific interactions within the LUSC microenvironment and to connect genomic alterations with immune signatures. Hierarchical clustering based on gene expression and mutational profiling revealed subtypes that were either immune defective or immune competent. We analyzed infiltrating stromal and immune cells to further characterize the tumor microenvironment. Elevated expression of macrophage 2 signature genes in the immune competent subtype confirmed that tumor-associated macrophages (TAM) linked inflammation and mutation-driven cancer. A negative correlation was evident between the immune score and the amount of somatic copy-number variation (SCNV) of immune genes ( = -0.58). The SCNVs showed a potential detrimental effect on immunity in the immune-deficient subtype. Knowledge of the genomic alterations in the tumor microenvironment could be used to guide design of immunotherapy options that are appropriate for patients with certain cancer subtypes. .
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http://dx.doi.org/10.1158/2326-6066.CIR-17-0453DOI Listing
July 2018

The Regulation of NRF2 by Nutrient-Responsive Signaling and Its Role in Anabolic Cancer Metabolism.

Antioxid Redox Signal 2018 12 16;29(17):1774-1791. Epub 2017 Oct 16.

Department of Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute , Tampa, Florida.

Significance: The stress responsive transcription factor nuclear factor erythroid 2 p45-related factor 2, or NRF2, regulates the expression of many cytoprotective enzymes to mitigate oxidative stress under physiological conditions. NRF2 is activated in response to oxidative stress, growth factor signaling, and changes in nutrient status. In addition, somatic mutations that disrupt the interaction between NRF2 and its negative regulator Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated 1 (KEAP1) commonly occur in cancer and are thought to promote tumorigenesis. Recent Advances: While it is well established that aberrant NRF2 activation results in enhanced antioxidant capacity in cancer cells, recent exciting findings demonstrate a role for NRF2-mediated metabolic deregulation that supports cancer cell proliferation.

Critical Issues: In this review, we describe how the NRF2-KEAP1 signaling pathway is altered in cancer, how NRF2 is regulated by changes in cellular metabolism, and how NRF2 reprograms cellular metabolism to support proliferation.

Future Directions: Future studies will delineate the NRF2-regulated processes critical for metabolic adaptation to nutrient availability, cellular proliferation, and tumorigenesis. Antioxid. Redox Signal. 00, 000-000.
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http://dx.doi.org/10.1089/ars.2017.7356DOI Listing
December 2018

Porcine endothelium induces DNA-histone complex formation in human whole blood: a harmful effect of histone on coagulation and endothelial activation.

Xenotransplantation 2016 11 10;23(6):464-471. Epub 2016 Sep 10.

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Neutrophils play a role in xenograft rejection. When neutrophils are stimulated, they eject the DNA-histone complex into the extracellular space, called neutrophil extracellular traps (NET). We investigated whether NET formation actively occurs in the xenograft and contributes to coagulation and endothelial activation.

Methods: Human whole blood was incubated with porcine aortic endothelial cells (pEC) from wild-type or α1,3-galactosyltransferase gene-knockout (GTKO) pigs. In the supernatant plasma from human blood, the level of the DNA-histone complex was measured by ELISA, and thrombin generation was measured using a calibrated automated thrombogram. Histone-induced tissue factor and adhesion molecule expression were measured by flow cytometry.

Results: pEC from both wild-type and GTKO pigs significantly induced DNA-histone complex formation in human whole blood. The DNA-histone complex produced shortened the thrombin generation time and clotting time. Histone alone dose-dependently induced tissue factor and adhesion molecule expression in pEC. Aurintricarboxylic acid pretreatment partially inhibited pEC-induced DNA-histone complex formation.

Conclusions: DNA-histone complex actively generated upon xenotransplantation is a novel target to inhibit coagulation and endothelial activation. To prevent tissue factor and adhesion molecule expression, a strategy to block soluble histone may be required in xenotransplantation.
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http://dx.doi.org/10.1111/xen.12264DOI Listing
November 2016

Metabolic Profiling Regarding Pathogenesis of Idiopathic Pulmonary Fibrosis.

J Proteome Res 2016 05 18;15(5):1717-24. Epub 2016 Apr 18.

Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital , 1174, Jung- Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do 420-767, Korea.

Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease characterized by fibrosis of the lung parenchyma and loss of lung function. IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair process including uncontrolled proliferation of lung (myo) fibroblasts and excessive deposition of extracellular matrix proteins in the interstitial space; however, the pathogenic pathways involved in IPF have not been fully elucidated. In this study, we attempted to characterize metabolic changes of lung tissues involved in the pathogenesis of IPF using gas chromatography-mass spectrometry-based metabolic profiling. Partial least-squares discriminant analysis (PLS-DA) model generated from metabolite data was able to discriminate between the control subjects and IPF patients (R(2)X = 0.37, R(2)Y = 0.613 and Q(2) (cumulative) = 0.54, receiver operator characteristic AUC > 0.9). We discovered 25 metabolite signatures of IPF using both univariate and multivariate statistical analyses (FDR < 0.05 and VIP score of PLS-DA > 1). These metabolite signatures indicated alteration in metabolic pathways: adenosine triphosphate degradation pathway, glycolysis pathway, glutathione biosynthesis pathway, and ornithine aminotransferase pathway. The results could provide additional insight into understanding the disease and potential for developing biomarkers.
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http://dx.doi.org/10.1021/acs.jproteome.6b00156DOI Listing
May 2016

Whole Cell Bioconversion of Ricinoleic Acid to 12-Ketooleic Acid by Recombinant Corynebacterium glutamicum-Based Biocatalyst.

J Microbiol Biotechnol 2015 Apr;25(4):452-8

Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 121-742, Republic of Korea.

The biocatalytic efficiency of recombinant Corynebacterium glutamicum ATCC 13032 expressing the secondary alcohol dehydrogenase of Micrococcus luteus NCTC2665 was studied. Recombinant C. glutamicum converts ricinoleic acid to a product, identified by gas chromatography/mass spectrometry as 12-ketooleic acid (12-oxo-cis-9-octadecenoic acid). The effects of pH, reaction temperature, and non-ionic detergent on recombinant C. glutamiucm whole cell bioconversion were examined. The determined optimal conditions for production of 12-ketooleic acid are pH 8.0, 35°C, and 0.05 g/l Tween80. Under these conditions, recombinant C. glutamicum produces 3.3 mM 12-ketooleic acid, with a 72% (mol/mol) maximum conversion yield, and 1.1 g/l/h volumetric productivity in 2 h; and 3.9 mM 12- ketooleic acid, with a 74% (mol/mol) maximum conversion yield, and 0.69 g/l/h maximum volumetric productivity in 4 h of fermentation. This study constitutes the first report of significant production of 12-ketooleic acid using a recombinant Corynebacterium glutamicum-based biocatalyst.
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http://dx.doi.org/10.4014/jmb.1501.01001DOI Listing
April 2015

Novel approach for analysis of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS-based lipidomics: lipid levels in asthmatics and corticosteroid-treated asthmatic patients.

J Proteome Res 2014 Sep 30;13(9):3919-29. Epub 2014 Jul 30.

College of Pharmacy, Seoul National University , 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.

To better understand the respiratory lipid phenotypes of asthma, we developed a novel method for lipid profiling of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS with an internal spectral library and high-throughput lipid-identifying software. The method was applied to BALF from 38 asthmatic patients (18 patients with nonsteroid treated bronchial asthma [NSBA] and 20 patients with steroid treated bronchial asthma [SBA]) and 13 healthy subjects (NC). We identified 69 lipids, which were categorized into one of six lipid classes: lysophosphatidylcholine (LPC), phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), sphingomyelin (SM) and triglyceride (TG). Compared with the NC group, the individual quantity levels of the six classes of lipids were significantly higher in the NSBA subjects. In the SBA subjects, the PC, PG, PS, SM, and TG levels were similar to the levels observed in the NC group. Using differentially expressed lipid species (p value < 0.05, FDR < 0.1 and VIP score of PLS-DA > 1), 34 lipid biomarker candidates with high prediction performance between asthmatics and controls were identified (AUROC > 0.9). These novel findings revealed specific characteristics of lipid phenotypes in asthmatic patients and suggested the importance of future research on the relationship between lipid levels and asthma.
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http://dx.doi.org/10.1021/pr5002059DOI Listing
September 2014

Metabolically engineered glucose-utilizing Shewanella strains under anaerobic conditions.

Bioresour Technol 2014 Feb 13;154:59-66. Epub 2013 Dec 13.

School of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan gwagi-ro, Buk-gu, Gwangju 500-712, Republic of Korea. Electronic address:

Comparative genome analysis of Shewanella strains predicted that the strains metabolize preferably two- and three-carbon carbohydrates as carbon/electron source because many Shewanella genomes are deficient of the key enzymes in glycolysis (e.g., glucokinase). In addition, all Shewanella genomes are known to have only one set of genes associated with the phosphotransferase system required to uptake sugars. To engineer Shewanella strains that can utilize five- and six-carbon carbohydrates, we constructed glucose-utilizing Shewanella oneidensis MR-1 by introducing the glucose facilitator (glf; ZMO0366) and glucokinase (glk; ZMO0369) genes of Zymomonas mobilis. The engineered MR-1 strain was able to grow on glucose as a sole carbon/electron source under anaerobic conditions. The glucose affinity (Ks) and glucokinase activity in the engineered MR-1 strain were 299.46 mM and 0.259 ± 0.034 U/g proteins. The engineered strain was successfully applied to a microbial fuel cell system and exhibited current generation using glucose as the electron source.
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http://dx.doi.org/10.1016/j.biortech.2013.12.025DOI Listing
February 2014

Comparative evaluation of runoff and water quality using HSPF and SWMM.

Water Sci Technol 2010 ;62(6):1401-9

Department of Environmental Science, Konkuk University, Seoul, Korea.

Stormwater pollution is the untreated contaminated water that drains into natural waterways from land uses within an urban catchment. Several studies have demonstrated the deterioration of water quality in receiving bodies of water caused by stormwater runoff. The data have reported that urban runoff play primary roles in degrading water quality in adjacent aquatic systems. The accurate estimation of non-pollutant loads from urban runoff and the prediction of water quality in receiving waters are important. The objective of this paper is to assess the applicability of the watershed scale hydrologic and water quality simulation models SWMM and HSPF to simulate the hydrology of a small watershed in the Han River Basin. Monitoring was performed in small scale watersheds, which is homogeneous land use. The applicability of SWMM and HSPF model was examined for small watersheds using hourly monitoring data. The results of SWMM were reasonably reflected with observed data in small scale urban area. HSPF model was effective at specifying parameters related to runoff and water quality when using hourly monitoring data. The watershed models used in this study adequately simulated watershed characteristics and are recommended to support watershed management.
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http://dx.doi.org/10.2166/wst.2010.302DOI Listing
December 2010

A multi-center, randomized, clinical study to compare the effect and safety of autologous cultured osteoblast(Ossron) injection to treat fractures.

BMC Musculoskelet Disord 2009 Feb 12;10:20. Epub 2009 Feb 12.

Department of Orthopedic Surgery, Catholic University College of Medicine, Seoul, Korea.

Background: We performed a multicenter, open, randomized, clinical study of autologous cultured osteoblast injection for long-bone fracture, to evaluate the fracture healing acceleration effect and the safety of autologous cultured osteoblasts.

Methods: Sixty-four patients with long-bone fractures were randomly divided into two groups, i.e. those who received autologous cultured osteoblast injection and those who received no treatment. The sum of the difference in the callus formation scores after four and eight weeks, was used as the first efficacy variable.

Results: The autologous cultured osteoblast injection group showed fracture healing acceleration of statistical significance, and there were no specific patient complications when using this treatment.

Conclusion: Autologous cultured osteoblast injection should therefore be considered as a successful treatment option for treating long-bone fracture.
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http://dx.doi.org/10.1186/1471-2474-10-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656455PMC
February 2009

Hematein inhibits atherosclerosis by inhibition of reactive oxygen generation and NF-kappaB-dependent inflammatory mediators in hyperlipidemic mice.

J Cardiovasc Pharmacol 2003 Aug;42(2):287-95

Department of Veterinary Pathology, College of Veterinary Medicine and Agricultural Biotechnology, Seoul National University, Suwon, Korea.

Hematein, a natural compound, is a known anti-inflammatory and antiatherogenic agent in the rabbit model. The authors investigated the effects of this compound on atherogenesis and possible mechanisms of the actions in the hyperlipidemic mice. Low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed a high-cholesterol diet alone for 8 weeks developed the fatty streak lesion in the aortic sinus, whereas this lesion was significantly reduced by hematein treatment without a change in plasma lipid levels compared with control mice. Hematein treatment reduced plasma levels of lipid peroxide and superoxide generation in LPS-stimulated peritoneal macrophage. Hematein treatment inhibited NF-kappaB-DNA binding activity in peritoneal macrophages from Ldlr-/- mice and the activation of NF-kappaB in RAW264.7 macrophages. This compound suppressed plasma nitrite/nitrate levels in Ldlr-/- mice and NO production and iNOS expression in LPS+IFNgamma-stimulated peritoneal macrophages. Hematein treatment also suppressed the activity of iNOS promoters in RAW264.7 macrophages, and reduced the plasma levels of TNF-alpha and IL-1beta and the production of these cytokines in LPS+IFNgamma-stimulated peritoneal macrophages. These results suggest that hematein inhibits atherosclerotic lesion formation, possibly by reducing proinflammatory mediators through a decrease in reactive oxygen species generation and NF-kappaB activation.
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http://dx.doi.org/10.1097/00005344-200308000-00019DOI Listing
August 2003