Branched-chain aminotransferases (BCAT) are enzymes that initiate the catabolism of branched-chain amino acids (BCAA), such as leucine, thereby providing macromolecule precursors; however, the function of BCATs in macrophages is unknown. Here we show that BCAT1 is the predominant BCAT isoform in human primary macrophages. We identify ERG240 as a leucine analogue that blocks BCAT1 activity. Sele...

Rho kinase signaling regulates inflammatory cell migration and chemokine production. We therefore investigated the mechanisms of Rho-kinase-dependent inflammation in lipopolysaccharide (LPS)-induced renal failure. C57/BL6 mice received intraperitoneal LPS with or without daily treatment with specific Rho kinase inhibitors (Y-27632 or HA-1077; 5 mg/kg). Rho kinase inhibitors were applied in a pr...

Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. The transcription factor nuclear factor-kappaB (NF-kappaB), which is inhibited by GCs, regulates numerous genes central to inflammation. In this study, the effects of stress, GCs, and NMDA receptors on lipop...

Ethanol and LPS are immunomodulators, whose actions are associated with the activation of the transcription factor, NF-kappaB, that mediates the expression of a number of rapid response genes involved in the whole body inflammatory response to injury, including transcriptional regulation of iNOS and COX-2. We investigated modulation by acute ethanol (EtOH) intoxication, LPS and LPS tolerance of...

Establishment of nitrogen-fixing symbiosis requires the recognition of rhizobial molecules to initiate the development of nodules. Using transcriptional profiling of roots inoculated with mutant strains defective in the synthesis of Nod Factor (NF), exopolysaccharide (EPS), or lipopolysaccharide (LPS), we identified 2,606 genes from common bean (Phaseolus vulgaris) that are differentially regul...

Matrix metalloproteinases (MMPs) are critical to vascular smooth muscle cell migration in vivo. The dysregulation of MMPs is involved in the pathogenesis of abnormal arterial remodeling, aneurysm formation and atherosclerotic plaque instability. It has been confirmed that lipopolysaccharides (LPS) constitute a strong risk factor for the developmen...

INTRODUCTION The objective of this study was to evaluate the interaction between ozone oxidative preconditioning and the anesthetic ketamine on cytoplasmic nuclear factor κB (NF-κB) levels in a rat endotoxic shock model. MATERIAL AND METHODS Forty Wistar rats were randomly divided into 5 groups: I - control group; II - rats intraperitoneally (i.p.) treated with LPS; III - rats treated with LP...

Increased plasma and hepatic TNF-alpha expression is well documented in patients with alcoholic hepatitis and is implicated in the pathogenesis of alcoholic liver disease. We have previously shown that monocytes from patients with alcoholic hepatitis show increased constitutive and LPS-induced NF-kappaB activation and TNF-alpha production. Our recent studies showed that chronic ethanol exposure...

When given in the presence of gamma interferon (IFN-gamma), otherwise nontoxic doses of lipopolysaccharide (LPS or endotoxin) become highly lethal for mice. The mechanisms of this synergistic toxicity are not known. We considered the possibility that an interaction between the LPS-induced NF-kappaB and IFN-gamma-induced JAK-STAT pathways at the pretranscriptional level may enhance the LPS-induc...

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. High-mobility group box 1 (HMGB1) serves as a late mediator of lethality in sepsis. We have reported that glucan phosphate (GP) attenuates cardiac dysfunction and increases survival in cecal ligation and puncture (CLP)-induced septic mice. In the present study, we examined the effect o...