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Peroxisome proliferator-activated receptor ligands for airway diseases?
  1. K Parameswaran
  1. Firestone Institute for Respiratory Health, St Joseph’s Healthcare and Department of Medicine, McMaster University, Hamilton, Ontario, Canadaparames{at}mcmaster.ca

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The peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors belonging to the hormone receptor family. The alpha and gamma subtypes are predominantly expressed in liver, muscle, and adipose tissues where, when activated by ligands such as glitazones, they regulate lipid metabolism. Using RT-PCR, Western blot analysis, and confocal microscopy, Patel and colleagues have shown, for the first time, the expresssion of these receptors on cultured human airway smooth muscle cells. In addition, activation of the gamma subtype by ciglitazone decreased the synthesis of GM-CSF (an eosinophil survival factor) and G-CSF (a neutrophil survival factor) by stimulated airway smooth muscle cells, demonstrating a potential anti-inflammatory role for this class of drugs in the airway. They also inhibited smooth muscle growth and promoted their apoptosis more potently than dexamethasone.

Since smooth muscle cells have a significant role in airway diseases such as asthma and COPD, PPAR gamma ligands may prove to be effective in regulating their function, particularly in the process of airway remodelling. Their role in regulating airway smooth muscle migration and controlling steroid insensitive airway inflammation needs further study.

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