PPARγ affects nitric oxide in human umbilical vein endothelial cells exposed to Porphyromonas gingivalis

Objective: Porphyromonas gingivalis induces nitric oxide (NO) synthesis in human umbilical vein endothelial cells (HUVECs). Peroxisome proliferator-activated receptor (PPAR gamma) has an anti-inflammation function, and its involvement in this NO induction process requires elucidation. Here, we focused on PPAR gamma expression in HUVECs exposed to P. gingivalis, and investigated its effects on NO synthesis. Materials and methods: HUVECs were time-dependently stimulated by P. gingivalis W83 for 0-24 h. PPAR gamma expression was assessed at the mRNA and protein levels, and PPAR gamma activation was measured using dual-luciferase reporter assays. NO synthesis and NO synthase (NOS) expression in response to P. gingivalis were examined in HUVECs pretreated with representative PPAR gamma agonist (15-deoxy-Delta 12,14-prostaglandin J(2) 10 mu M) or antagonist (GW9662 10 mu M). In addition, NO synthesis and NOS expression in the P. gingivalis infected and control groups were detected. Results: The PPAR gamma mRNA level in HUVECs increased after exposure to P. gingivalis for 1 h and its protein level increased at 2 h. Luciferase-induced PPAR gamma increased in P. gingivalis-exposed HUVECs. NO synthesis in the infected group at 4 h, and in the PPAR gamma-activated group at 8 h, was higher than that in controls. Inducible NOS increased in the infected and PPAR gamma-activated groups at 4 and 8 h. The total endothelial NOS (eNOS) and phospho-eNOS levels were lower in the infected group than controls, but did not change in the PPAR gamma-activated group. Conclusions: Activated PPAR gamma induces NO generation through the NOS pathway in HUVECs exposed to P. gingivalis. (C) 2016 Elsevier Ltd. All rights reserved.