PPARgamma agonists upregulate the barrier function of tight junctions via a PKC pathway in human nasal epithelial cells.
Peroxisome proliferator activated (PPAR)gamma 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 PPAR gamma agonists on the tight junctional barrier of human nasal epithelial cells (HNECs), hTERT-transfected HNECs, which highly express both PPAR gamma and tight junction proteins, were treated with the PPAR gamma agonists rosiglitazone and troglitazone. Treatment with the PPAR gamma 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 PPAR gamma 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 PPAR gamma antagonists GW9662 and T0070907, but also the panPKC inhibitor GF109203X. These findings suggest that PPAR gamma 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.
Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Noriko
N
Ogasawara
Takashi
T
Kojima
Mitsuru
M
Go
Tsuyoshi
T
Ohkuni
Jun-ichi
J
Koizumi
Ryuta
R
Kamekura
Tomoyuki
T
Masaki
Masaki
M
Murata
Satoshi
S
Tanaka
Jun
J
Fuchimoto
Tetsuo
T
Himi
Norimasa
N
Sawada
D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009297:Nasal Mucosa / Q000166:cytology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D019108:Tight Junctions / Q000378:metabolism*; D000077288:Troglitazone
D002839:Chromans; D047495:PPAR gamma; D034741:RNA, Small Interfering; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011493:Protein Kinase C; D000077288:Troglitazone