The IL-33/ST2 Pathway in Cerebral Malaria.

Interleukin-33 (IL-33) is an immunomodulatory cytokine which plays critical roles in tissue function and immune-mediated diseases. IL-33 is abundant within the brain and spinal cord tissues where it acts as a key cytokine to coordinate the exchange between the immune and central nervous system (CNS). In this review, we report the recent advances to our knowledge regarding the role of IL-33 and of its receptor ST2 in cerebral malaria, and in particular, we highlight the pivotal role that IL-33/ST2 signaling pathway could play in brain and cerebrospinal barriers permeability.

Regulation of IL (Interleukin)-33 Production in Endothelial Cells via Kinase Activation and Fas/CD95 Upregulation.

Objective: The occurrence of new blood vessel formation in the lungs of asthmatic patients suggests a critical role for airway endothelial cells (ECs) in the disease. IL-33 (Interleukin-33)-a cytokine abundantly expressed in human lung ECs-recently emerged as a key factor in the development of allergic diseases, including asthma. In the present study, we evaluated whether mouse and human ECs exposed to the common allergen produce IL-33 and characterized the activated signaling pathways.

Environmental and genetic contribution in airway epithelial barrier in asthma pathogenesis.

Purpose Of Review: To examine the recent, most relevant genetic and epigenetic modifications of the epithelial barrier in response to the environmental factors, including allergens, viruses, and pollutants, susceptible to participate to asthma.

Recent Findings: IL-33 and TSLP gene polymorphisms are found in almost all asthma studies. Recent data have highlighted a new population of innate lymphoid cells, activated by these two cytokines, and mediating type 2 innate immunity dependent asthma.

Fenofibrate inhibits endothelin-1 expression by peroxisome proliferator-activated receptor α-dependent and independent mechanisms in human endothelial cells.

Objective: Dyslipidemia contributes to endothelial dysfunction in type 2 diabetes mellitus. Fenofibrate (FF), a ligand of the peroxisome proliferator-activated receptor-α (PPARα), has beneficial effects on microvascular complications. FF may act on the endothelium by regulating vasoactive factors, including endothelin-1 (ET-1).

PPAR SUMOylation: some useful experimental tips.

Studies on the regulation of nuclear receptors, such as the peroxisome proliferator-activated receptors (PPARs), are important to enhance our understanding of their molecular, cellular, and physiological behavior. A decade ago, it was shown that the SUMOylation pathway plays a very important role in the regulation of transcription factor activity. The SUMOylation process involves the covalent binding of SUMO protein to the target protein.

SUMOylation of human peroxisome proliferator-activated receptor alpha inhibits its trans-activity through the recruitment of the nuclear corepressor NCoR.

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is a key regulator of genes implicated in lipid homeostasis and inflammation. PPARalpha trans-activity is enhanced by recruitment of coactivators such as SRC1 and CBP/p300 and is inhibited by binding of corepressors such as NCoR and SMRT. In addition to ligand binding, PPARalpha activity is regulated by post-translational modifications such as phosphorylation and ubiquitination.

Selective PPAR modulators, dual and pan PPAR agonists: multimodal drugs for the treatment of type 2 diabetes and atherosclerosis.

More than 70% of patients with Type 2 diabetes mellitus (T2DM) die because of cardiovascular diseases. Current therapeutic strategies are based on separate treatment of insulin resistance and dyslipidaemia. Development of drugs with multimodal activities should improve management of the global cardiovascular risk of T2DM patients and result in better patient compliance.

Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway.

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase used in the prevention of cardiovascular disease (CVD). In addition to their cholesterol-lowering activities, statins exert pleiotropic antiinflammatory effects, which might contribute to their beneficial effects not only on CVD but also on lipid-unrelated immune and inflammatory diseases, such as rheumatoid arthritis, asthma, stroke, and transplant rejection. However, the molecular mechanisms involved in these antiinflammatory properties of statins are unresolved.

PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a.

Vascular SMC proliferation is a crucial event in occlusive cardiovascular diseases. PPARalpha is a nuclear receptor controlling lipid metabolism and inflammation, but its role in the regulation of SMC growth remains to be established. Here, we show that PPARalpha controls SMC cell-cycle progression at the G1/S transition by targeting the cyclin-dependent kinase inhibitor and tumor suppressor p16(INK4a) (p16), resulting in an inhibition of retinoblastoma protein phosphorylation.

Different ways to regulate the PPARalpha stability.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor. PPARalpha regulates lipid and glucose metabolism and controls the inflammatory response. Recently, we have shown that PPARalpha is a short-lived protein degraded by the ubiquitin-proteasome system.

The protein kinase C signaling pathway regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha.

Peroxisome proliferator-activated receptor (PPAR) alpha is a nuclear receptor implicated in several physiological processes such as lipid and lipoprotein metabolism, glucose homeostasis, and the inflammatory response. PPARalpha is activated by natural fatty acids and synthetic compounds like fibrates. PPARalpha activity has been shown to be modulated by its phosphorylation status.

Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. Three PPARs isoforms have been characterized: PPARalpha, beta/delta and gamma. As other nuclear receptors, the PPARs are organized in distinct functional domains: A/B, C or DNA binding domain (DBD), D, E or ligand binding domain (LBD) and F.

Peroxisome proliferator-activated receptor alpha (PPARalpha ) turnover by the ubiquitin-proteasome system controls the ligand-induced expression level of its target genes.

Peroxisome proliferator activated-receptor alpha (PPARalpha) is a ligand-activated transcription factor belonging to the nuclear receptor family. PPARalpha is implicated in the regulation of lipid and glucose metabolism and in the control of inflammatory response. Recently, it has been demonstrated that a number of nuclear receptors are degraded by the ubiquitin-proteasome pathway.