Prostaglandin and PPAR control of immune cell function.

Abstract

Peroxisome proliferator-activated receptors (PPARs) belong to a superfamily of intracellular ligand-activated receptors. These receptors are also transcription factors exerting their regulatory functions directly at the gene level.1 PPARs appear to act as messengers responsible for translating a wide variety of stimuli into changes in gene expression and cellular differentiation pathways. They were originally identified as molecular targets for compounds that induce an increase in the size and number of hepatic and renal peroxisomes. Peroxisomes are single-membrane organelles present in nearly all eukaryotic cells and carry out metabolic peroxidation reactions, primarily the β-oxidation of fatty acids. Peroxisome proliferators increase the capacity of peroxisomes to metabolize fatty acids via increased expression of the enzymes required for β-oxidation.2,3 Currently three subtypes of mammalian PPARs have been identified, termed α, δ (originally termed β) and γ, encoded by different genes and showing distinct tissue distributions. Both PPAR-α and PPAR-γ act as regulators of lipid metabolism; PPAR-α plays a crucial role in hepatic liver metabolism and PPAR-γ participates in adipocyte differentiation and function. No specific function has yet been identified for PPAR-δ, although it has a very wide distribution, can be activated by prostacyclin, may be involved in the control of cellular development and is potentially involved in the pathogenesis of tumours such as in colorectal cancer.4