Angiotensin II type 1-receptor antagonism prevents type IIA secretory phospholipase A2-dependent lipid peroxidation.

Accumulation and modification of low density lipoproteins (LDL) within the vessel wall represent key events in atherogenesis. Secretory phospholipase A2 type IIA (sPLA2-IIA) modulates the enzymatic process of LDL-modification and was recently identified as an independent predictor of coronary events in patients with coronary artery disease (CAD). Angiotensin II (ANG II) type 1 (AT1)-receptor blockade reduces LDL-modification and atherosclerotic plaque formation in rodent and primate models of atherosclerosis.

Hypoxia increases group IIA phospholipase A(2) expression under inflammatory conditions in rat renal mesangial cells.

Hypoxia evokes a common mechanism of oxygen sensing mediated by hypoxia-inducible transcription factors (HIF) in many mammalian cells. This study investigated the effect of hypoxia on group-IIA secretory phospholipase A(2) (sPLA(2)-IIA) expression in renal mesangial cells. Stimulation of cells with IL-1beta under normoxic conditions (21% O(2)) is known to induce expression and secretion of the group sPLA(2)-IIA.

Characterization and differentiation-dependent regulation of secreted phospholipases A in human keratinocytes and in healthy and psoriatic human skin.

Secreted phospholipases A2 (sPLA2) expressed in the skin are thought to be involved in epidermal barrier homeostasis as well as in inflammation. We investigated the expression of the novel sPLA2 subtypes in human skin at mRNA and protein levels in the epidermis and primary keratinocytes from healthy human skin, and in skin sections from patients with psoriasis, where the integrity of the epidermis is drastically affected. Immunofluorescence studies using specific antibodies for the different sPLA2 enzymes show that sPLA2-IB, -IIF, and -X are predominantly expressed in suprabasal layers, whereas sPLA2-V and -IID are detected in the basal and spinous layers.

Elevated secretory non-pancreatic type II phospholipase A2 serum activity is associated with impaired endothelial vasodilator function in patients with coronary artery disease.

Low-grade inflammatory activity is associated with an increased risk for ischaemic coronary events. sPLA(2) (secretory non-pancreatic type II phospholipase A(2)) serum activity is increased in chronic inflammatory diseases and may also contribute to atherogenesis. Since the endothelium is a major target for inflammatory cytokines, we hypothesized that elevated serum activity of sPLA(2) is associated with an impaired vasodilator function in patients with documented CAD (coronary artery disease).

Amelioration of endotoxin-induced sepsis in rats by membrane anchored lipid conjugates.

Objective: In the pathogenesis of septic shock, caused by either bacterial toxins or trauma, increased production of multiple proinflammatory mediators, such as phospholipase A(2) (PLA(2)), cytokines, and chemokines, is known to be of major importance. The present study was undertaken to investigate the influence of a newly designed extracellular PLA(2) inhibitor (ExPLI) on synthesis of proinflammatory mediators and mortality rate in a rat sepsis model.

Design: Prospective, randomized animal study.

Differentiation-dependent regulation of secreted phospholipases A2 in murine epidermis.

The action of secreted phospholipases A2 in skin is thought to be essential for epidermal barrier homeostasis. The incomplete knowledge of presence and functions of the novel secreted phospholipase A2 subtypes in skin prompted us to explore their expression in epidermis and primary keratinocytes from murine neonatal skin. We detected secreted phospholipases A2-IB, -IIA, -IIC, -IID, -IIE, -IIF, -V, -X, and -XII.

Potentiation of tumor necrosis factor alpha-induced secreted phospholipase A2 (sPLA2)-IIA expression in mesangial cells by an autocrine loop involving sPLA2 and peroxisome proliferator-activated receptor alpha activation.

In rat mesangial cells, exogenously added secreted phospholipases A2 (sPLA2s) potentiate the expression of pro-inflammatory sPLA2-IIA first induced by cytokines like tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta. The transcriptional pathway mediating this effect is, however, unknown. Because products of PLA2 activity are endogenous activators of peroxisome proliferator-activated receptor alpha (PPAR alpha, we postulated that sPLA2s mediate their effects on sPLA2-IIA expression via sPLA2 activity and subsequent PPAR alpha activation.

Secreted phospholipases A2 induce the expression of chemokines in microvascular endothelium.

Acute respiratory distress syndrome (ARDS) is characterized by alterations in microvascular permeability. In ARDS secreted phospholipase A(2) (sPLA(2)) IB and IIA are found to be highly upregulated. In this study, we therefore investigated the influence of exogenously added sPLA(2)-IB and sPLA(2)-IIA on the production of chemokines and adhesion molecules in lung microvascular endothelial cells (LMVEC).

Hyperosmotic stress induces phosphorylation of cytosolic phospholipase A(2) in HaCaT cells by an epidermal growth factor receptor-mediated process.

Cytosolic phospholipase A(2) (cPLA(2)) is an enzyme involved in the formation of proinflammatory mediators by catalyzing the release of arachidonic acid, thereby mediating eicosanoid biosynthesis. Using HaCaT keratinocytes as a model system, we present experimental evidence that in these cells, cPLA(2) is constitutively phosphorylated and that the degree of phosphorylation dramatically increases in cells under hyperosmotic stress induced by sorbitol. In parallel, a rapid release of arachidonic acid followed by prostaglandin E(2) formation was detected.

Dephosphorylation of endothelial nitric oxide synthase contributes to the anti-angiogenic effects of endostatin.

Endostatin is an anti-angiogenic factor that inhibits endothelial cell (EC) migration and induces EC apoptosis. Because nitric oxide (NO) plays a key role in vascular endothelial growth factor (VEGF)-induced angiogenesis, we hypothesized that endostatin interferes with the activation of the endothelial NO synthase (eNOS). Human recombinant endostatin significantly reduced VEGF-induced NO-release, which suggests that endostatin inhibits eNOS activation.

Potentiation of TNF-alpha-stimulated group IIA phospholipase A(2) expression by peroxisome proliferator-activated receptor alpha activators in rat mesangial cells.

Natural activators of peroxisome proliferator-activated receptors (PPAR) are lipid metabolites, including those produced by phospholipases A(2) (PLA(2)). In glomerular mesangial cells, the secreted group IIA PLA(2) (sPLA(2)-IIA), which is thought to be a crucial factor in pathologic processes in the kidney, may provide free fatty acids and eicosanoids directly or indirectly, by activating a cytosolic PLA(2). The scope of this study was to investigate whether synthetic PPAR(alpha) activators have an effect on sPLA(2)-IIA mRNA expression in rat mesangial cells, thus constituting a feedback modulation of sPLA(2)-IIA transcription.

Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages: regulation by Group IV cytosolic phospholipase A2, but not by Group V and Group IIA secretory phospholipase A2.

Lipopolysaccharide (LPS) induces a delayed release (lag phase of 2-4 h) of arachidonic acid (AA) and prostaglandin (PG) D2 in rat liver macrophages. Group IV cytosolic phospholipase A2 (cPLA2) becomes phosphorylated within minutes after the addition of LPS. The phosphorylated form of cPLA2 shows an enhanced in vitro activity.