Receptors, Immunologic

Publication Title: 
Circulation

BACKGROUND: Human atherosclerotic lesions contain elevated levels of urokinase plasminogen activator (uPA), expressed predominantly by macrophages. METHODS AND RESULTS: To test the hypothesis that macrophage-expressed uPA contributes to the progression and complications of atherosclerosis, we generated transgenic mice with macrophage-targeted overexpression of uPA. The uPA transgene was bred into the apolipoprotein E-null background, and transgenic mice and nontransgenic littermate controls were fed an atherogenic diet.

Author(s): 
Cozen, Aaron E.
Moriwaki, Hideaki
Kremen, Michal
DeYoung, Mary Beth
Dichek, HelÈn L.
Slezicki, Katherine I.
Young, Stephen G.
VÈniant, Murielle
Dichek, David A.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

BACKGROUND: Aging is a complex multifactorial process characterized by accumulation of deleterious changes in cells and tissues, progressive deterioration of structural integrity and physiological function across multiple organ systems, and increased risk of death. METHODS: We conducted a review of the scientific literature on the relationship of advanced glycation end products (AGEs) with aging. AGEs are a heterogeneous group of bioactive molecules that are formed by the nonenzymatic glycation of proteins, lipids, and nucleic acids.

Author(s): 
Semba, Richard D.
Nicklett, Emily J.
Ferrucci, Luigi
Publication Title: 
Journal of Lipid Research

Cholesterol-laden macrophages are the hallmark of atherogenesis. The class B scavenger receptor, CD36, binds oxidized low density lipoprotein (OxLDL), is found in atherosclerotic lesions, and is upregulated by OxLDL. We tested the effects of alpha-tocopherol (AT) enrichment of human monocyte-derived macrophages on CD36 expression and cholesteryl ester accumulation. Monocytes isolated from normal volunteers were cultured into macrophages. Macrophages were enriched overnight with various doses of AT (25, 50, and 100 microM).

Author(s): 
Devaraj, S.
Hugou, I.
Jialal, I.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 +/- 3% of the glucan phosphate and 20 +/- 7% of the laminarin remained in the serum. Scleroglucan was rapidly absorbed and eliminated.

Author(s): 
Rice, Peter J.
Adams, Elizabeth L.
Ozment-Skelton, Tammy
Gonzalez, Andres J.
Goldman, Matthew P.
Lockhart, Brent E.
Barker, Luke A.
Breuel, Kevin F.
Deponti, Warren K.
Kalbfleisch, John H.
Ensley, Harry E.
Brown, Gordon D.
Gordon, Siamon
Williams, David L.
Publication Title: 
Current Opinion in Pharmacology

A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells, and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4), HMGB1 activates vascular endothelial cells and macrophages/monocytes to express proinflammatory cytokines, chemokines and adhesion molecules.

Author(s): 
Li, Wei
Sama, Andrew E.
Wang, Haichao
Publication Title: 
Rheumatology (Oxford, England)

OBJECTIVE: To investigate whether advanced glycation end products (AGEs) induce the expression of IL-6 and IL-8 through the receptor for AGEs (RAGE)-activated pathways in human OA chondrocytes. METHODS: OA chondrocytes were stimulated with AGE-modified BSA (AGE-BSA). Gene expression of IL-6 and IL-8 was quantified by TaqMan assays and the production was determined using ELISAs. Immunoblotting was used to analyse the activation of mitogen-activated protein kinases (MAPKs) and the degradation of IκBα. Activation of NF-κB was determined using an ELISA.

Author(s): 
Rasheed, Zafar
Akhtar, Nahid
Haqqi, Tariq M.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

A plethora of work implicates important effects of the vitamin A derivative retinoic acid (RA) in myeloid differentiation, whereas fewer studies explore the role of RA in lymphoid cells. Most work on lymphoid cells has focused on the influence of RA on CD4 T cells. Little information about the role of RA in CD8 T cell differentiation is available, and even less on cell-intrinsic effects in the CD8 T cell. This study explores the role of RA in effector and memory differentiation in a cell-intrinsic manner in the context of vaccinia virus infection.

Author(s): 
Allie, S. Rameeza
Zhang, Weijun
Tsai, Ching-Yi
Noelle, Randolph J.
Usherwood, Edward J.
Publication Title: 
Brain Research

Different mechanisms have been suggested to contribute to isoflurane-mediated neuroprotection. Previous studies have suggested that the protein Slit can abrogate neuronal death in mixed neuronal-glial cultures exposed to oxygen-glucose deprivation (OGD) and reperfusion (OGD/R). We hypothesized that isoflurane increases the expression of Slit and its receptor Robo when cortical neurons are exposed to OGD/R.

Author(s): 
Zhao, Xiao-Chun
Zhang, Li-Min
Li, Qiang
Tong, Dong-Yi
Fan, Long-Chang
An, Ping
Wu, Xiu-Ying
Chen, Wei-Min
Zhao, Ping
Wang, Jian
Publication Title: 
Molecular Therapy: The Journal of the American Society of Gene Therapy

Many metabolic diseases are caused by defects in the metabolic pathways in the liver. Others result from the absence of specific proteins normally produced and secreted by the liver. Because these metabolic disorders are usually caused by single gene defect, they are ideal candidates for gene therapy. We have previously shown that mouse liver can be transfected by mechanically massaging the liver (MML) after intravenous injection of naked plasmid DNA.

Author(s): 
Liu, Feng
Lei, Jing
Vollmer, Regis
Huang, Leaf
Publication Title: 
Circulation Research

Obstructive sleep apnea, a syndrome leading to recurrent intermittent hypoxia (IH), has been associated previously with hypercholesterolemia, independent of underlying obesity. We examined the effects of experimentally induced IH on serum lipid levels and pathways of lipid metabolism in the absence and presence of obesity. Lean C57BL/6J mice and leptin-deficient obese C57BL/6J-Lep(ob) mice were exposed to IH for five days to determine changes in serum lipid profile, liver lipid content, and expression of key hepatic genes of lipid metabolism.

Author(s): 
Li, Jianguo
Thorne, Laura N.
Punjabi, Naresh M.
Sun, Cheuk-Kwan
Schwartz, Alan R.
Smith, Philip L.
Marino, Rafael L.
Rodriguez, Annabelle
Hubbard, Walter C.
O'Donnell, Christopher P.
Polotsky, Vsevolod Y.

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