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Recent Patents on Inflammation & Allergy Drug Discovery
ISSN (Print): 1872-213X
ISSN (Online): 2212-2710
VOLUME: 8
ISSUE: 2
DOI: 10.2174/1872213X08666140623114845      Price:  $100









Modulatory Effects of Peroxisome Proliferator-Activated Receptor-γ on CXCR3 Chemokines

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Author(s): Silvia Martina Ferrari, Alessandro Antonelli, Andrea Di Domenicantonio, Andreina Manfredi, Clodoveo Ferri and Poupak Fallahi
Pages 132-138 (7)
Abstract:
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.
Keywords:
CXCL9, CXCL10, CXCL11, CXCR3, pioglitazone, PPAR-gamma agonists, PPAR-gamma antagonists, rosiglitazone.
Affiliation:
Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, I-56126, Pisa, Italy.