Circulating pathogen associated molecular pattern - Binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: Implications for cellular Toll-like receptor activity

被引:36
作者
Jialal, I. [1 ,2 ]
Rajamani, U. [1 ]
Adams-Huet, B. [3 ]
Kaur, H. [1 ]
机构
[1] Univ Calif Davis, Med Ctr, Dept Pathol, Div Endocrinol Diabet & Metab,Lab Atherosclerosis, Sacramento, CA 95817 USA
[2] VA Med Ctr, Sacramento, CA USA
[3] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Div Biostat, Dallas, TX USA
关键词
PAMP-binding proteins; sCD14; HMGB-1; Metabolic syndrome; Toll-like receptors; INSULIN-RESISTANCE; SOLUBLE CD14; LIPOPOLYSACCHARIDE; ACTIVATION; OBESITY; EXPRESSION; LBP; MONOCYTES; CELLS; INFLAMMATION;
D O I
10.1016/j.atherosclerosis.2014.06.022
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: The Metabolic Syndrome, (MetS) a global epidemic, is a state of low grade chronic inflammation and confers an increased risk for diabetes and CVD. We have previously reported increased activity of the pathogen recognition receptors, Toll-like receptors (TLRs), TLR2 and TLR4 in MetS. We hypothesized that increased TLR activity in MetS is due in part to increased levels of circulating PAMP -binding proteins, soluble CD14 (sCD14), lipopolysaccharide binding protein (LBP) and the damage associated molecular pattern (DAMP), High Mobility Group Box protein 1 (HMGB-1). Methods: We measured sCD14, LBP and HMGB-1 in fasting plasma from nascent MetS (n = 37) and healthy control subjects (n = 32) by ELISA. We also investigated the effects of sCD14 and LBP on TLR4 activity in human aortic endothelial cells (HAECs). Results: Following adjustment for body mass index and waist circumference, sCD14, LBP and HMGB-1 levels remained significantly increased in MetS. Also their levels increased with increasing numbers of MetS risk factors. Only sCD14 correlated significantly with monocyte TLR4 protein and activity. None of these soluble biomarkers correlated with TLR2 protein. Both sCD14 and HMGB-1 correlated significantly with HOMA-IR. In LPS primed HAECs, sCD14 compared to LBP, resulted in a greater increase in both TLR4 abundance and inflammatory biomediators (NF-kappa B, IL-1 beta, IL-8 and TNF-alpha). Conclusion: Thus, we make the novel observation that sCD14 reflects increased monocyte TLR4 protein and activity in nascent MetS and by contributing to increased cellular inflammation could explain, in part, the increased risk for diabetes and CVD. Published by Elsevier Ireland Ltd.
引用
收藏
页码:182 / 187
页数:6
相关论文
共 40 条
[1]   Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity [J].
Alberti, K. G. M. M. ;
Eckel, Robert H. ;
Grundy, Scott M. ;
Zimmet, Paul Z. ;
Cleeman, James I. ;
Donato, Karen A. ;
Fruchart, Jean-Charles ;
James, W. Philip T. ;
Loria, Catherine M. ;
Smith, Sidney C., Jr. .
CIRCULATION, 2009, 120 (16) :1640-1645
[2]   Metabolic endotoxemia initiates obesity and insulin resistance [J].
Cani, Patrice D. ;
Amar, Jacques ;
Iglesias, Miguel Angel ;
Poggi, Marjorie ;
Knauf, Claude ;
Bastelica, Delphine ;
Neyrinck, Audrey M. ;
Fava, Francesca ;
Tuohy, Kieran M. ;
Chabo, Chantal ;
Waget, Aurelie ;
Delmee, Evelyne ;
Cousin, Beatrice ;
Sulpice, Thierry ;
Chamontin, Bernard ;
Ferrieres, Jean ;
Tanti, Jean-Francois ;
Gibson, Glenn R. ;
Casteilla, Louis ;
Delzenne, Nathalie M. ;
Alessi, Marie Christine ;
Burcelin, Remy .
DIABETES, 2007, 56 (07) :1761-1772
[3]   High Glucose Induces Toll-Like Receptor Expression in Human Monocytes Mechanism of Activation [J].
Dasu, Mohan R. ;
Devaraj, Sridevi ;
Zhao, Ling ;
Hwang, Daniel H. ;
Jialal, Ishwarlal .
DIABETES, 2008, 57 (11) :3090-3098
[4]   Increased Toll-Like Receptor (TLR) Activation and TLR Ligands in Recently Diagnosed Type 2 Diabetic Subjects [J].
Dasu, Mohan R. ;
Devaraj, Sridevi ;
Park, Samuel ;
Jialal, Ishwarlal .
DIABETES CARE, 2010, 33 (04) :861-868
[5]   Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes [J].
Devaraj, S. ;
Dasu, M. R. ;
Park, S. H. ;
Jialal, I. .
DIABETOLOGIA, 2009, 52 (08) :1665-1668
[6]   Direct demonstration of an antiinflammatory effect of simvastatin in subjects with the metabolic syndrome [J].
Devaraj, Sridevi ;
Chan, Emily ;
Jialal, Ishwarlal .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (11) :4489-4496
[7]   Determinants of Serum Concentrations of Lipopolysaccharide-Binding Protein (LBP) in the Adult Population: The Role of Obesity [J].
Gonzalez-Quintela, Arturo ;
Alonso, Manuela ;
Campos, Joaquin ;
Vizcaino, Luis ;
Loidi, Lourdes ;
Gude, Francisco .
PLOS ONE, 2013, 8 (01)
[8]   Diagnosis and management of the metabolic syndrome - An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement [J].
Grundy, SM ;
Cleeman, JI ;
Daniels, SR ;
Donato, KA ;
Eckel, RH ;
Franklin, BA ;
Gordon, DJ ;
Krauss, RM ;
Savage, PJ ;
Smith, SC ;
Spertus, JA ;
Costa, F .
CIRCULATION, 2005, 112 (17) :2735-2752
[9]   Increased Toll-like receptor (TLR) mRNA expression in monocytes is a feature of metabolic syndrome in adolescents [J].
Hardy, O. T. ;
Kim, A. ;
Ciccarelli, C. ;
Hayman, L. L. ;
Wiecha, J. .
PEDIATRIC OBESITY, 2013, 8 (01) :e19-e23
[10]   The nuclear protein HMGB1 as a proinflammatory mediator [J].
Harris, HE ;
Andersson, U .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (06) :1503-1512