Modulatory Effects of Peroxisome Proliferator-Activated Receptor-γ on CXCR3 Chemokines
Silvia Martina Ferrari, Alessandro Antonelli, Andrea Di Domenicantonio, Andreina Manfredi, Clodoveo Ferri and Poupak Fallahi
Affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, I-56126, Pisa, Italy.
Keywords: CXCL9, CXCL10, CXCL11, CXCR3, pioglitazone, PPAR-gamma agonists, PPAR-gamma antagonists, rosiglitazone.
An increasing body of evidence shows the importance of the chemokine (C-X-C motif) receptor (CXCR)3 and
cognate chemokines (C-X-C motif) ligand (CXCL)9, CXCL10 and CXCL11 in the T helper 1 immune response, and in
inflammatory diseases such as bowel inflammatory disorders, allograft rejection, thyroid autoimmune disorders, vascular
and renal inflammation, and others. Peroxisome proliferator-activated receptor (PPAR)-γ agonists show a strong inhibitory
effect on the expression and production of CXCR3 chemokines in vitro, in various kinds of cells, such as denditric
cells, monocytes, macrophages, endothelial and vascular smooth muscle cells, intestinal cells, thyrocytes, fibroblasts,
preadypocytes and mesangial cells, and in vivo in animal models. As rosiglitazone has recently been linked to a higher
risk of heart failure, stroke, and all-cause mortality in old patients, it has been interrupted from the European market. On
the contrary, the safety profile of pioglitazone seems favorable. However, further studies are ongoing to explore the use of
new PPAR-γ agonists in the treatment of the above mentioned inflammatory disorders, and many interesting patents have
been recently applied.
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