Protein Kinase C Is Involved in the Induction of ATP-Binding Cassette Transporter A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human Macrophages.

The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression.

Protein Kinase C Is Involved in the Induction of ATP-Binding Cassette Transporter A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human Macrophages.

The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression.

The expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 in human macrophages is inhibited by the anti-atherogenic cytokine transforming growth factor-β and requires Smads, p38 mitogen-activated protein kinase and c-Jun.

Atherosclerosis is an inflammatory disorder of the vasculature that is orchestrated by the action of cytokines. Macrophages play a prominent role in all stages of this disease, including foam cell formation, production of reactive oxygen species, modulation of the inflammatory response and the regulation of the stability of atherosclerotic plaques. The role of the matrix metalloproteinase family in the control of plaque stability is well established.

A novel role for c-Jun N-terminal kinase and phosphoinositide 3-kinase in the liver X receptor-mediated induction of macrophage gene expression.

Liver X receptors (LXRs) are ligand-dependent transcription factors that are activated by metabolites of cholesterol, oxysterols, and a number of synthetic agonists. LXRs play potent anti-atherogenic roles in part by stimulating the efflux of cholesterol from macrophage foam cells. The LXR-induced expression of ATP-binding cassette transporter (ABC)-A1 and Apolipoprotein E (ApoE) in macrophages is essential for the stimulation of cholesterol efflux and the prevention of atherosclerotic development.

The TNF-like protein 1A-death receptor 3 pathway promotes macrophage foam cell formation in vitro.

TNF-like protein 1A (TL1A), a TNF superfamily cytokine that binds to death receptor 3 (DR3), is highly expressed in macrophage foam cell-rich regions of atherosclerotic plaques, although its role in foam cell formation has yet to be elucidated. We investigated whether TL1A can directly stimulate macrophage foam cell formation in both THP-1 and primary human monocyte-derived macrophages with the underlying mechanisms involved. We demonstrated that TL1A promotes foam cell formation in human macrophages in vitro by increasing both acetylated and oxidized low-density lipoprotein uptake, by enhancing intracellular total and esterified cholesterol levels and reducing cholesterol efflux.

Requirement for nuclear factor kappa B signalling in the interleukin-1-induced expression of the CCAAT/enhancer binding protein-delta gene in hepatocytes.

Elevated circulating levels of acute phase proteins (APP) are associated with inflammation and inflammatory disorders such as cardiovascular disease. APP are mainly synthesised by hepatocytes and their transcription is induced by pro-inflammatory cytokines such as interleukin-1 (IL-1). The molecular mechanisms underlying the IL-1-induced expression of key transcription factors implicated in the regulation of APP are poorly understood.

The tumour necrosis factor-alpha-mediated suppression of the CCAAT/enhancer binding protein-alpha gene transcription in hepatocytes involves inhibition of autoregulation.

Tumour necrosis factor-alpha (TNF-alpha) is a key regulator of the immune and inflammatory responses along with numerous other cellular changes during physiological and pathophysiological conditions. The cellular actions of TNF-alpha are associated with both the activation and the inhibition of gene transcription. In contrast to gene activation, the mechanisms underlying the TNF-alpha-mediated transcriptional inhibition remain largely unclear.

Protein kinase CK2, an important regulator of the inflammatory response?

Casein kinase 2 (CK2) is a highly conserved serine-threonine kinase that uses both adenosine triphosphate and guanosine triphosphate as phosphate donors. This constitutively active and ubiquitously expressed enzyme is often present as a tetrameric holoenzyme complex of two catalytic subunits (alpha and/or alpha') and two regulatory beta subunits. The enzyme is known to phosphorylate more than 300 substrates and controls a wide range of processes, including the regulation of cell cycle, apoptosis, transformation, and circadian rhythm.

Antimicrobial susceptibility pattern of clinical isolates of Pseudomonas aeruginosa in a tertiary care hospital.

Background And Purpose: Pseudomonas aeruginosa is an important cause of morbidity and mortality in hospitalized, critically ill patients and patients with underlying medical conditions such as cystic fibrosis, neutropenia, and iatrogenic immunosuppression. The prevalence of multiresistant P. aeruginosa isolates has been increasing.

The role of transforming growth factor-beta in atherosclerosis.

Transforming growth factor-beta (TGF-beta) plays a pivotal role in a range of biological processes, including the control of cellular proliferation and differentiation, regulation of tissue repair and extracellular matrix accumulation, and modulation of the immune and inflammatory responses. The role of TGF-beta in the pathogenesis of atherosclerosis, which is widely perceived as a form of chronic inflammation, has been the subject of debate for a number of years. A pro-atherogenic role was suspected because of its ability to promote fibrosis and to inhibit endothelial regeneration.

Transforming growth factor-beta-induced expression of the apolipoprotein E gene requires c-Jun N-terminal kinase, p38 kinase, and casein kinase 2.

Objective: The cytokine transforming growth factor-beta (TGF-beta) and apolipoprotein E (apoE) play potent antiatherogenic roles. Despite such importance, the mechanisms underlying the regulation of apoE expression by TGF-beta have not been characterized and were therefore investigated.

Methods And Results: Using THP-1 cell line as a model system, with key findings confirmed in primary cultures, we show that TGF-beta induces the expression of apoE, and this is prevented by pharmacological inhibitors of c-Jun N-terminal kinase (JNK), p38 kinase, and casein kinase 2 (CK2).

Disseminated invasive aspergillosis in an apparently immunocompetent host.

Aspergillosis is a spectrum of diseases caused by members of the genus Aspergillus that continues to pose a significant threat to immunocompromised, organ transplant, neutropenic and cancer patients. In view of increasing risk factors leading to invasive aspergillosis, it is imperative for clinicians to be familiar with the clinical presentation, diagnostic methods and management of the disease. We describe a 34-year-old immunocompetent male patient receiving chemotherapy for Aspergillus fumigatus infection that had disseminated to lung, liver and spleen.

Interferon-gamma stimulates the expression of the inducible cAMP early repressor in macrophages through the activation of casein kinase 2. A potentially novel pathway for interferon-gamma-mediated inhibition of gene transcription.

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that modulates the immune function, cell proliferation, apoptosis, macrophage activation, and numerous other cellular responses. These biological actions of IFN-gamma are characterized by both the activation and the inhibition of gene transcription. Unfortunately, in contrast to gene activation, the mechanisms through which the cytokine suppresses gene transcription remain largely unclear.