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Targeting PPAR receptors in the airway for the treatment of inflammatory lung disease
Author(s) -
Belvisi Maria G,
Mitchell Jane A
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00373.x
Subject(s) - peroxisome proliferator activated receptor , nuclear receptor , receptor , inflammation , ppar agonist , lipid metabolism , medicine , rosiglitazone , angiogenesis , immunology , cancer research , fibrosis , transcription factor , bioinformatics , biology , pharmacology , gene , biochemistry
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. PPARgamma regulates several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of genes involved in lipid biosynthesis and glucose metabolism. However, more recently PPARgamma, PPARalpha and PPARbeta/delta agonists have been demonstrated to exhibit anti-inflammatory and immunomodulatory properties thus opening up new avenues for research. The actions of PPARgamma and PPARalpha activation are thought to be due to their ability to down regulate pro-inflammatory gene expression and inflammatory cell functions, and as such makes them an attractive target for novel drug intervention. Interestingly, PPARbeta/delta has been shown to be involved in wound healing, angiogenesis, lipid metabolism and thrombosis. In this review we will focus on the data describing the beneficial effects of these ligands in the airway and in the pulmonary vasculature and in vivo in animal models of allergic and occupational asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. A clinical trial is underway to examine the effect of rosiglitazone in asthma patients and the outcome of this trial is awaited with much anticipation. In conclusion, PPARs are novel targets for lung disease and continued work with these ligands may result in a potential new treatment for chronic inflammatory lung diseases.