PPARγ agonists upregulate the barrier function of tight junctions via a PKC pathway in human nasal epithelial cells

Peroxisome proliferator activated (PPAR)γ plays a critical role in the control of not only adipocyte differentiation, lipid metabolism and immunity but also the barrier functions of epithelial and endothelial cells. In the present study, to investigate effects of PPARγ agonists on the tight junctional barrier of human nasal epithelial cells (HNECs), hTERT-transfected HNECs, which highly express both PPARγ and tight junction proteins, were treated with the PPARγ agonists rosiglitazone and troglitazone. Treatment with the PPARγ agonists enhanced the barrier function of hTERT-transfected HNECs together with the upregulation of tight junction molecules claudin-1 and -4, occludin, and tricellulin at the transcriptional level. A significant increase of tight junction strands was also observed after treatment with rosiglitazone. Treatment with PPARγ agonists induced the activity of phospho-PKC in hTERT-transfected HNECs. The upregulation of the tight junction molecules in hTERT-transfected HNECs by rosiglitazone was inhibited by not only PPARγ antagonists GW9662 and T0070907, but also the panPKC inhibitor GF109203X.These findings suggest that PPARγ agonists upregulate the barrier function of tight junctions of human nasal epithelial cells via a PKC signaling pathway and could be novel drugs for protection against inhaled substances and pathogens in the airway epithelium of human nasal mucosa.