Lipopolysaccharide-induced activation of NF-κB non-canonical pathway requires BCL10 serine 138 and NIK phosphorylations.

Background And Aims: B-cell lymphoma/leukemia (BCL)-10 and reactive oxygen species mediate two pathways of NF-κB (RelA) activation by lipopolysaccharide (LPS) in human colonic epithelial cells. The pathway for LPS activation of RelB by the non-canonical pathway (RelB) in non-myeloid cells was not yet reported, but important for understanding the range of potential microbial LPS-induced effects in inflammatory bowel disease.

Methods: Experiments were performed in human colonic epithelial cells and in mouse embryonic fibroblasts deficient in components of the IkappaB kinase (IKK) signalosome, in order to detect mediators of the non-canonical pathway of NF-κB activation, including nuclear RelB and p52 and phospho- and total NF-κB inducing kinase (NIK).

Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent.

Background: Platelet-activating factor (PAF), a potent proinflammatory phospholipid mediator, has been implicated in inducing intestinal inflammation in diseases such as inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). However, its mechanisms of inducing inflammatory responses are not fully understood. Therefore, studies were designed to explore the mechanisms of PAF-induced inflammatory cascade in intestinal epithelial cells.

Regulation of monocarboxylate transporter 1 (MCT1) promoter by butyrate in human intestinal epithelial cells: involvement of NF-kappaB pathway.

Butyrate, a short chain fatty acid (SCFA) produced by bacterial fermentation of undigested carbohydrates in the colon, constitutes the major fuel for colonocytes. We have earlier shown the role of apically localized monocarboxylate transporter isoform 1 (MCT1) in transport of butyrate into human colonic Caco-2 cells. In an effort to study the regulation of MCT1 gene, we and others have cloned the promoter region of the MCT1 gene and identified cis elements for key transcription factors.

Development, evaluation, and application of a highly sensitive microtiter plate ELISA for human Bcl10 protein.

Bcl10 (B-cell CLL/lymphoma 10) is a 233 amino acid CARD (caspase recruitment domain)-containing cellular protein, increasingly recognized as a mediator of NFkappaB activation in non-immune, as well as immune cells. Due to the importance of Bcl10 in diverse cell types, we developed a solid-phase, enzyme-linked immunosorbent (ELISA) assay to precisely measure Bcl10 in small volume cell lysates, using recombinant Bcl10 to standardize the assay. Standard curve measures Bcl10 from 0.

Carrageenan reduces bone morphogenetic protein-4 (BMP4) and activates the Wnt/beta-catenin pathway in normal human colonocytes.

Carrageenans are highly sulfated polysaccharides that are widely used as food additives in the Western diet, in order to improve the texture of processed foods. Although native and degraded carrageenans induce colonic ulcerations, polyps, and colorectal tumors in animal models, very little is known about the effects of carrageenan on human colonocytes. We evaluated effects of lambda-carrageenan (lambdaCGN) on the normal human colonocyte cell line NCM460, using a concentration of 1 mug/ml, about less than one tenth the average daily exposure to carrageenan in the Western diet.

Utility of screening tools for the prediction of low bone mass in African American men.

Introduction: Osteoporosis remains under-diagnosed, particularly in African American men, despite the availability of reliable diagnostic tests. In women, several screening tools, including heel ultrasound and clinical assessment tools, reliably predict low bone mass, however the usefulness of these screening tools in African American men is unknown. The aim of this study was to determine the utility of screening tools, namely heel ultrasound, the osteoporosis self-assessment tool (OST), weight-based criterion (WBC) and body mass index (BMI), in screening for low bone mass in African American men.

CREB gene transcription factors: role in molecular mechanisms of alcohol and drug addiction.

This article presents the proceedings of a symposium presented at the meeting of the Research Society on Alcoholism, held in Vancouver, British Columbia, Canada, in June 2004. The organizers and chairpersons were Subhash C. Pandey and Fulton Crews.