Activation of κ-opioid receptor inhibits inflammatory response induced by sodium palmitate in human umbilical vein endothelial cells. (October 2021)

• Record Type: Journal Article
• Authors: Zhang, Shumiao; Yang, Fan; Shi, Rui; Liu, Chaoyang; Zhao, Lei; Gu, Xiaoming; Liu, Yinji; Fu, Feng; Feng, Na; Liu, Yali; Jia, Min; Fan, Rong; Yang, Lu; Li, Jun; Li, Juan; Pei, Jianming
• Is Part Of: Cytokine. Volume 146(2021)
• Publication Date: 2021-10
• Subjects: κ-opioid receptor -- Hyperlipidemia -- Inflammatory factors -- Inflammation -- Adherent molecules; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2021.155659
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Sodium palmitate induces inflammatory response in HUVECs. κ-opioid receptor activation ameliorates sodium palmitate-induced inflammation. κ-opioid receptor activation inhibits the inflammation via PI3K/Akt/eNOS pathway. Abstract: Objectives: The current study aims to investigate the effect of κ-opioid receptor (κ-OR) activation on sodium palmitate (SP)-induced human umbilical vein endothelial cells (HUVECs) inflammatory response and elucidate the underlying mechanisms. Methods: A hyperlipidemic cell model was established and treated with κ-OR agonist (U50, 488H), and antagonist (norbinaltorphimine, nor-BNI), or inhibitors targeting PI3K, Akt or eNOS (LY294002, MK2206-2HCl or L-NAME, respectively). Furthermore, the expression levels of NLRP3, caspase-1, p-Akt, Akt, p-eNOS, and total eNOS were evaluated. Additionally, the production of reactive oxygen species, and levels of inflammatory factors, such as TNF-α, IL-1β, IL-6, IL-1 and adhesion molecules, such as ICAM-1, VCAM-1, P-selectin, and E-selectin were determined. The adherence rates of the neutrophils and monocytes were assessed as well. Results: The SP-induced hyperlipidemic cell model demonstrated increased expression of NLRP3 and caspase-1 proteins ( P < 0.05) and elevated ROS levels ( P < 0.01), and decreased phosphorylated-Akt and phosphorylated-eNOS expression ( P < 0.05). In addition, SP significantly increased TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, P-selectin, and E-selectin levels ( P < 0.01), decreased IL-10 levels ( P < 0.01), and increased the adhesion rates of monocytes and neutrophils ( P < 0.01). The SP-induced inflammatory response in HUVECs was ameliorated by κ-OR agonist, U50, 488H. However, the protective effect of U50, 488H was abolished by κ-OR antagonist, nor-BNI, and inhibitors of PI3K, Akt and eNOS. Conclusion: Our findings suggest that κ-OR activation inhibits SP-induced inflammation by activating the PI3K/Akt/eNOS signaling pathway.