Peroxisome proliferator-activated receptors in inflammation control

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated tr anscription factors belonging to the nuclear receptor superfamily. PPAR alp ha is highly expressed in liver, skeletal muscle, kidney, heart and the vas cular wall. PPAR gamma is predominantly detected in adipose tissue, intesti ne and macrophages. PPARs are activated by fatty-acid derivatives and pharm acological agents such as fibrates and glitazones which are specific for PP AR alpha and PPAR gamma respectively. PPARs regulate lipid and lipoprotein metabolism, glucose homeostasis, cell proliferation and differentiation, an d apoptosis. PPAR alpha controls intra- and extracellular lipid metabolisms whereas PPAR gamma triggers adipocyte differentiation and promotes lipid s torage. In addition, PPARs also modulate the inflammatory response. PPAR ac tivators have been shown to exert anti-inflammatory activities in various c ell types by inhibiting the expression of proinflammatory genes such as cyt okines, metalloproteases and acute-phase proteins. PPARs negatively regulat e the transcription of inflammatory response genes by antagonizing the AP-1 , nuclear factor-kappaB (NF-kappaB), signal transducer and activator of tra nscription and nuclear factor of activated T-cells signalling pathways and by stimulating the catabolism of proinflammatory eicosanoids. These recent findings indicate a modulatory role PPARs in inflammation with potential th erapeutical applications in chronic inflammatory diseases.