Kynurenic acid attenuates pro-inflammatory reactions in lipopolysaccharide-stimulated endothelial cells through the PPARδ/HO-1-dependent pathway

Kynurenic acid (KA) regulates energy homeostasis and alleviates inflammation in adipose tissue but how KA affects the atherosclerotic response in HUVECs remains unclear. We evaluated the effects of KA on lipopoly-saccharide (LPS)-induced inflammation and apoptosis in HUVECs. KA enhanced peroxisome proliferator-activated receptor delta (PPARd) expression in HUVECs and THP-1 cells and suppressed LPS-induced atherosclerotic responses through PPARd-mediated signaling. Moreover, KA treatment mitigated LPS-induced phosphorylation of nuclear factor kappa B and pro-inflammatory cytokine release in HUVECs and THP-1 cells, and down-regulated adhesion molecules in HUVECs and adhesion of THP-1 cells to HUVECs following LPS treatment. KA treatment decreased LPS-induced inflammation and apoptosis, and also promoted heme oxygenase (HO)-1 expression, which suppresses inflammation in HUVECs. Suppression of PPARd or HO-1 expression markedly mitigated the effects of KA on atherosclerotic responses in HUVECs. Thus, KA attenuates LPS-induced atherosclerotic responses by suppressing inflammation via the PPARd/HO-1-dependent pathway.