High Glucose Level Disturbs the Resveratrol-Evoked Curtailment of CX3CL1CX3CR1 Signaling in Human Placental Circulation

Abstract EN

Hyperglycemia-induced hyperactivity of chemokine CX3CL1 (fractalkine) occurs in the human placenta.

Anti-inflammatory/antioxidant activities of resveratrol (3,5,4′-trihydroxy-trans-stilbene) are related to the modulation of chemokine CX3CL1 and its receptor, CX3CR1, signaling pathways.

We examined the influence of high glucose (25 mmol/L glucose; HG group; N=36) on resveratrol-mediated effects on CX3CL1 and TNF-α production by the placental lobule, CX3CR1 expression and contents of CX3CR1, TNF-α receptor 1 (TNFR1), and NF-κB proteins in placental tissue.

The placental lobules perfused under normoglycemic conditions formed the control NG group (N=36).

Resveratrol (50 and 100 μM; subgroups B and C) administered into the perfusion fluid lowered the production of both CX3CL1 and TNF-α.

The reductions in CX3CL1 levels were more evident in the NG group.

CX3CR1 expression was significantly higher in the NG subgroups B and C compared to the HG subgroups B and C (385.2 and 426.5% versus 199.3 and 282.4%, resp.).

An increase in CX3CR1 protein content in placental lysates was observed in the NG subgroups B and C.

Also, resveratrol significantly decreased NF-κBp65 protein content only in the NG group, not affecting hyperglycemia-elicited TNFR1 upregulation.

In conclusion, euglycemia assures optimal effects of resveratrol pertaining to CX3CL1/CX3CR1 signaling in the placenta.

Future studies on resveratrol are needed, especially those including maternal-fetal risk assessments.