Abstract P417: Proinflammatory Cytokine Production By Activated T Cells Cultured In PVAT-conditioned Media From Dahl S Rats On A High Fat Diet Correlates With The Development Of Hypertension

Abstract

There is growing evidence to suggest an association between the immune system and hypertension. Our previous studies demonstrated that soluble mediators from mesenteric perivascular adipose tissue (mPVAT) influence T cell function during hypertension. Specifically, we found that conditioned media from mPVAT derived from hypertensive rats on high fat (HF) diet for 10 wk promoted expression of pro-inflammatory cytokines by activated T cells. Accordingly, the purpose of the present study was to identify the timepoint at which this effect begins. Toward this end, we cultured anti-CD3/anti-CD28-activated splenocytes in mPVAT-conditioned media (PVAT-CM) from Dahl S rats on either control or HF diet for 8 wks. Data show that mPVAT-CM from either control or HF diet animals suppressed IL-2 induction by T cells activated for 24 h by 60% (control: 190.9±15.6 pg/ml vs. HF: 224.3±12.7 pg/ml) compared to the group without CM (580±4.2 pg/ml). We also collected supernatants after 96 h of activation and performed a multiplex cytokine assay. Our data show that while the induction of the pro-inflammatory cytokine IL-17a is greatly increased by PVAT-CM from Dahl S rats on HF diet for 10 wks (29340±5570 pg/ml) compared to control diet (14080±2410 pg/ml), this was not observed at the 8-wk timepoint (HF: 5970±893 pg/ml; control diet: 5995±675 pg/ml). Similarly, PVAT-CM from Dahl S rats on HF diet for 10 wks (653±66 pg/ml) also greatly increased induction of GM-CSF compared to PVAT-CM from rats on control diet (381±57.9 pg/ml)—this difference was not observed at 8 wks (HF: 1274±269 pg/ml; control diet: 1276±58 pg/ml). Overall, the data demonstrate that mPVAT-CM from Dahl S rats on a HF diet for 10 wks, but not 8 wks, significantly increases proinflammatory cytokine production by activated splenic T cells, which correlates with the timepoint at which blood pressure becomes elevated in this model.