Prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk.

Background: Prostaglandin D2 (PGD2) and cysteinyl leukotrienes (cysLTs) are lipid mediators derived from mast cells, which activate TH2 cells. The combination of PGD2 and cysLTs (notably cysteinyl leukotriene E4 [LTE4]) enhances TH2 cytokine production. However, the synergistic interaction of cysLTs with PGD2 in promoting TH2 cell activation is still poorly understood.

An audit of pneumococcal and hepatitis vaccination in an outpatient HIV clinic.

Background: HIV-positive adults are at risk of vaccine preventable infections including Streptococcus pneumoniae, hepatitis A virus (HAV) and hepatitis B virus (HBV). Uptake of immunisations in HIV patients is suboptimal despite evidence of efficacy.

Methods: An audit was made of the vaccination records in 200 adult HIV-positive regular clinic attendees, with a CD4+ count >200 cells μL(-1).

Significance of isolated reactive treponemal chemiluminescence immunoassay results.

Background: Isolated reactive serum treponemal chemiluminescence immunoassay (CIA) specimens cause clinical uncertainty.

Methods: Sera were screened by CIA, and reactive samples underwent reflex testing with rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and fluorescent treponemal antibody absorption (FTA Abs) assays. Samples reactive only on the CIA were deemed "isolated" reactive CIA samples.

Leukotriene E4 activates human Th2 cells for exaggerated proinflammatory cytokine production in response to prostaglandin D2.

PGD(2) exerts a number of proinflammatory responses through a high-affinity interaction with chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and has been detected at high concentrations at sites of allergic inflammation. Because cysteinyl leukotrienes (cysLTs) are also produced during the allergic response, we investigated the possibility that cysLTs may modulate the response of human Th2 cells to PGD(2). PGD(2) induced concentration-dependent Th2 cytokine production in the absence of TCR stimulation.

Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophils.

D prostanoid receptor 2 (DP₂) [also known as chemoattractant receptor-homologous molecule expressed on T helper 2 (Th2) cells (CRTH2)] is selectively expressed by Th2 lymphocytes, eosinophils, and basophils and mediates recruitment and activation of these cell types in response to prostaglandin D₂ (PGD₂). (5-Fluoro-2-methyl-3-quinolin-2-ylmethylindo-1-yl)-acetic acid (OC000459) is an indole-acetic acid derivative that potently displaces [³H]PGD₂ from human recombinant DP₂ (K(i) = 0.013 μM), rat recombinant DP₂ (K(i) = 0.

Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells.

PGD2, produced by mast cells, has been detected in high concentrations at sites of allergic inflammation. It can stimulate vascular and other inflammatory responses by interaction with D prostanoid receptor (DP) and chemoattractant receptor-like molecule expressed on Th2 cells (CRTH2) receptors. A significant role for PGD2 in mediating allergic responses has been suggested based on the observation that enhanced eosinophilic lung inflammation and cytokine production is apparent in the allergen-challenged airways of transgenic mice overexpressing human PGD2 synthase, and PGD2 can enhance Th2 cytokine production in vitro from CD3/CD28-costimulated Th2 cells.

Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2.

Prostaglandin D2 (PGD2) acting at the CRTH2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells) has been linked with a variety of allergic and other inflammatory diseases. We describe a family of indole-1-sulfonyl-3-acetic acids that are potent and selective CRTH2 antagonists that possess good oral bioavailability. The compounds may serve as novel starting points for the development of treatments of inflammatory disease such as asthma, allergic rhinitis, and atopic dermatitis.

Identification of G-protein-coupled receptors involved in inflammatory disease by genetic association studies.

G-protein-coupled receptors are not only highly tractable drug targets but also attractive candidates for genetic association studies because they are more polymorphic than most other classes of gene and these polymorphisms frequently lead to functional changes in the levels of expression or biological activity that can predispose to common diseases. A large-scale study to identify functional variants in G-protein-coupled receptors associated with inflammatory diseases has highlighted a spectrum of novel biological insights that range from identifying the involvement of orphan receptors in certain diseases through to highlighting new therapeutic indications for existing drugs.

Quantitative morphometry of lupus nephritis: the significance of collagen, tubular space, and inflammatory infiltrate.

Background: Lupus nephritis encompasses a wide range of parenchymal injuries and severity. Better predictors of outcome are needed for patients newly diagnosed with lupus nephritis, so that an appropriate management strategy may be selected.

Methods: A single-center cohort of first renal biopsies for lupus nephritis was chosen.

Antibacterial activities and characterization of novel inhibitors of LpxC.

Lipid A is the hydrophobic anchor of lipopolysaccharide (LPS) and forms the major lipid component of the outer monolayer of the outer membrane of gram-negative bacteria. Lipid A is required for bacterial growth and virulence, and inhibition of its biosynthesis is lethal to bacteria. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metalloenzyme that catalyzes the second step in the biosynthesis of lipid A.