High glucose reduces resveratrol‐dependent disruption of CX3CL1/CX3CR1 signaling in human placental circulation

Abstract

Upregulated activity of chemokine CX3CL1 (fractalkine) and abnormal expression of its sole receptor (CX3CR1) have been reported in many pro‐inflammatory conditions, including diabetes. Resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) possesses anti‐inflammatory and antioxidant properties related to its interference with NF‐κB (nuclear factor kappa‐beta) signaling pathway, which regulates the expression of various genes involved in inflammation, including CX3CL1. In this study, we examined influence of resveratrol on CX3CL1 production in extra corporeally perfused human term placental lobules under hyperglycemic (glucose 25 mmol/l; group I; N = 24) and normal (glucose 5 mmol/l; group II; N = 24) conditions. During the 150 min of perfusion, including the initial 30‐min adaptive phase, basal (immediately before administration of LPS) and LPS‐evoked (10 ng/ml) CX3CL1 secretion into the fetal side placental circulation was examined quantitatively in perfusion fluid samples using ELISA. After 60 min of perfusion, resveratrol (10~100μM) was added into the perfusion fluid. There were no significant differences between the studied groups in respect of the mean concentration of CX3CL1 (both basal and LPS‐evoked) in the samples collected before administration of resveratrol. Higher doses (50~100μM) of resveratrol produced significant (p < 0.05) reductions in CX3CL1 level in the perfusion fluid in both groups. However, significantly stronger (p < 0.02) reduction was observed in group II, compared to group I (2.37‐ vs. 1.64‐fold decrease, respectively). In conclusion, optimal anti‐inflammatory effects of resveratrol pertained to CX3CL1/CX3CR1 signaling in placental circulation should be expected under euglycemic conditions.Support or Funding InformationSupported by WUM grant: 2M2‐N‐15