%0 Journal Article
%T A Role for Peroxisome Proliferator-Activated Receptors in the Immunopathology of Schistosomiasis?
%A Barrie J. Anthony
%A Jeremy T. Allen
%A Yuesheng S. Li
%A Donald P. McManus
%J PPAR Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/128068
%X Peroxisome proliferator-activated receptors (PPARs) have been demonstrated to have a role in immune regulation. In general, they are anti-inflammatory and promote Th2 type responses, and they are associated with the alternative activation of macrophages. Interestingly, helminth infections, such as the schistosome blood flukes that cause schistosomiasis, are characterised by a Th2 response and the accumulation of alternative activated macrophages. This would suggest that at some level, PPARs could have a role in the modulation of the immune response in schistosomiasis. This paper discusses possible areas where PPARs could have a role in this disease. 1. Introduction The peroxisome proliferator-activated receptors (PPARs) are a group within the 48 transcription factors of the nuclear hormone receptor family involved in lipid metabolism and inflammation [1]. To be transcriptionally active, they require hetrodimerisation with the retinoid X receptor (RXR) to which the resulting heterodimers bind with peroxisome proliferator-response elements (PPREs) on DNA after activation by a ligand-to-modulate transcription [2]. The PPREs are located at the 5¡ä end of the target gene and consist of a repeat sequence¡ªAGGTCA¡ªseparated by one nucleotide [3]. The binding to the PPRE is orientated with PPAR at the 5¡ä end and RXR towards the 3¡ä end [2]. For transcriptional control to occur, the PPAR/RXR heterodimers have to interact with coactivators or suppressors for stimulation or inhibition of target-gene expression, respectively [2]. The PPARs can also block transcription of other genes by interacting with other transcription factors by non-genomic transrepression, whereby they inhibit transcription by preventing dissociation of corepressors or sequester co-activators needed for binding of the transcription factor to the DNA [4]. There are 3 isoforms of the PPAR receptors, PPAR¦Á, PPAR¦Â/¦Ä, and PPAR¦Ã [5]. PPAR¦Á is expressed in the liver, brown fat, heart, and skeletal muscle which have high levels of fatty acid catabolism, while PPAR¦Ã is expressed in adipose tissue, the colon, and in macrophages, it is the major regulator in adipocyte differentiation and is a determinant in insulin sensitivity [3]. PPAR¦Â/¦Ä is ubiquitously expressed and is thought to have a role in metabolic disorders [3]. Polyunsaturated fatty acids and eicosanoids act as natural ligands for these receptors; however, synthetic ligands exist such as fibrates that target PPAR¦Á and the thiazolidinediones that target PPAR¦Ã [3]. PPARS have been demonstrated to be important in a number of different disease states
%U http://www.hindawi.com/journals/ppar/2012/128068/