Authors: Edwards, Laura J.; Constantinescu, Cris S.

Source: Inflammation & Allergy - Drug Targets (Formerly Current Drug Targets - Inflammation & Allergy), Volume 8, Number 3, July 2009 , pp. 182-190(9)

Publisher: Bentham Science Publishers

Abstract:

Platelet activating factor (PAF) is a phospholipid mediator of inflammation that is released early in inflammation by a variety of cell types. PAF acts largely by binding to its receptor, PAF-R, a G-protein coupled receptor found on a variety of cells, including cells of the immune system.

PAF has been implicated in the pathogenesis of asthma and allergic conditions, but its role in autoimmune conditions has been less extensively investigated. Here, we review the accumulating evidence for the role of PAF/PAF-R pathway in autoimmune diseases. We describe studies showing up-regulation of PAF-R in inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis and review the evidence from the use of PAF-R antagonists. We describe results of experimental models of inflammatory diseases that point to a role for PAF/PAF-R pathway including those using PAF-R antagonists and those employing PAF-R knockout mice and knockout mice for cytosolic phospholipase2.

Recent experiments from our laboratory show that PAF/PAF-R pathway may influence T cell responses and favour the Th17 phenotype (in which T cells produce tissue destructive proinflammatory cytokine IL-17).

The PAF/PAF-R pathway is a promising target for pharmacological intervention in autoimmune diseases.

Keywords: Platelet activating factor; platelet activating factor receptor; autoimmunity

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152809788681010

Publication date: 2009-07-01

More about this publication?

• Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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