Toll-Like Receptor 2

Publication Title: 
Biogerontology

The aim of the present study was to determine Toll-like receptor (TLR)-2 and TLR-4 membrane expression on the major peritoneal leukocyte populations throughout the aging process, including subjects that had achieved exceptional longevity. ICR (CD1) female mice of different ages: adult (44 +/- 4 weeks), old (69 +/- 4), very old (92 +/- 4) and extreme long-lived (125 +/- 4), were used.

Author(s): 
Arranz, Lorena
De Castro, Nuria M.
Baeza, Isabel
De la Fuente, MÛnica
Publication Title: 
PloS One

Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA), a single dose of alpha,beta-arteether (ART) with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE) or ART+curcumin (AC) treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation.

Author(s): 
Vathsala, Palakkod G.
Dende, Chaitanya
Nagaraj, Viswanathan Arun
Bhattacharya, Debapriya
Das, Gobardhan
Rangarajan, Pundi N.
Padmanaban, Govindarajan
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: 
The Journal of Clinical Endocrinology and Metabolism

CONTEXT: Type 1 diabetes (T1DM) is associated with increased cardiovascular mortality. It is a pro-inflammatory state as evidenced by increased circulating biomarkers and monocyte activity. The toll-like receptors (TLRs) are pattern recognition receptors, expressed abundantly on monocytes. TLR2 and TLR4 are important in atherosclerosis. However, there is a paucity of data examining TLR2 and TLR4 expression in T1DM and examining its contribution to the proinflammatory state.

Author(s): 
Devaraj, Sridevi
Dasu, Mohan R.
Rockwood, Jason
Winter, William
Griffen, Steven C.
Jialal, Ishwarlal
Publication Title: 
International Immunopharmacology

We have identified potent monocyte/macrophage activating bacterial lipoproteins within commonly used immune enhancing botanicals such as Echinacea, American ginseng and alfalfa sprouts. These bacterial lipoproteins, along with lipopolysaccharides, were substantially more potent than other bacterially derived components when tested in in vitro monocyte/macrophage activation systems.

Author(s): 
Pugh, Nirmal D.
Tamta, Hemlata
Balachandran, Premalatha
Wu, Xiangmei
Howell, J'Lynn
Dayan, Franck E.
Pasco, David S.
Publication Title: 
Diabetes

OBJECTIVE: Hyperglycemia-induced inflammation is central in diabetes complications, and monocytes are important in orchestrating these effects. Toll-like receptors (TLRs) play a key role in innate immune responses and inflammation. However, there is a paucity of data examining the expression and activity of TLRs in hyperglycemic conditions. Thus, in the present study, we examined TLR2 and TLR4 mRNA and protein expression and mechanism of their induction in monocytic cells under high-glucose conditions.

Author(s): 
Dasu, Mohan R.
Devaraj, Sridevi
Zhao, Ling
Hwang, Daniel H.
Jialal, Ishwarlal
Publication Title: 
Endocrinology

Toll-like receptors (TLRs) are key innate immune sensors of endogenous damage signals and play an important role in inflammatory diseases like diabetes and atherosclerosis. Pioglitazone (PIO), a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, has been reported to be an antiinflammatory agent. Thus, in the present study, we examined the antiinflammatory effects of PIO on TLR2 and TLR4 expression in human monocytes exposed to Pam3CSK4 (Pam; TLR2 ligand) and purified lipopolysaccharide (LPS; TLR4 ligand) using flow cytometry and real-time RT-PCR.

Author(s): 
Dasu, Mohan R.
Park, Samuel
Devaraj, Sridevi
Jialal, Ishwarlal
Publication Title: 
Cytokine

Among the chemokines, members of the CXC family include IP-10 (interferon-gamma induced protein of 10kDa). Elevated serum IP-10 levels have been shown in diabetes. However, there is a paucity of data examining the sources and regulation of IP-10 under hyperglycemic conditions and this was the overall aim of the study. Type 1 diabetes (T1DM) is a pro-inflammatory state. We previously demonstrated increased toll like receptor (TLR) 2 and 4 activation in monocytes of T1DM patients.

Author(s): 
Devaraj, Sridevi
Jialal, Ishwarlal
Publication Title: 
Diabetologia

AIMS/HYPOTHESIS: Type 1 diabetes is a proinflammatory state characterised by increased levels of circulating biomarkers of inflammation and monocyte activity. We have shown increased Toll-like receptor 2 (TLR2) and TLR4 expression and signalling in monocytes from type 1 diabetic patients. Several endogenous ligands of TLR2 and TLR4 have been identified; however, there is a paucity of data on levels of these endogenous ligands in diabetes.

Author(s): 
Devaraj, S.
Dasu, M. R.
Park, S. H.
Jialal, I.
Publication Title: 
Thrombosis and Haemostasis

High-mobility group box 1 protein (HMGB1), an abundant nuclear protein, was recently established as a proinflammatory mediator of experimental sepsis. Although extracellular HMGB1 has been found in atherosclerotic plaques, its potential role in the pathogenesis of atherothrombosis remains elusive. In the present study, we determined whether HMGB1 induces tissue factor (TF) expression in vascular endothelial cells (ECs) and macrophages. Our data showed that HMGB1 stimulated ECs to express TF (but not TF pathway inhibitor) mRNA and protein in a concentration- and time-dependent manner.

Author(s): 
Lv, Ben
Wang, Haichao
Tang, Yiting
Fan, Zhang
Xiao, Xianzhong
Chen, Fangping

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