Polydatin and Resveratrol Inhibit the Inflammatory Process Induced by Urate and Pyrophosphate Crystals in THP-1 Cells

Abstract

Resveratol (RES) and its natural precursor polydatin (PD) are polyphenols that may display a broad variety of beneficial effects including anti-inflammatory properties. This study aimed to investigate the role of RES and PD in the inflammatory process induced by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in vitro. A monocytic cell line (THP-1) was primed for 3 hours with phorbol myristate acetate (100 ng/mL) and stimulated with synthetic MSU (0.05 mg/mL) and CPP (0.025 mg/mL) crystals. RES and PD were added to cultures concurrently with the crystals, or as 2-hour pretreatment. The effect of the two polyphenols was evaluated on intracellular and extracellular IL-1β levels, NACHT-LRRPYD-containing protein-3 (NLRP3) inflammasome expression, reactive oxygen species (ROS) and nitric oxide (NO) production, and the assessment of crystal phagocytosis. RES and PD strongly inhibited IL-1β induced by crystals after cell pretreatment. Cell pretreatment was effective also in reducing IL-1 mRNA expression while no effect was observed on NLRP3 gene expression. RES and PD had no effect on crystal phagocytosis when used as pretreatment. Both polyphenols were significantly effective in inhibiting ROS and NO production. Our results demonstrated that RES and PD are effective in inhibiting crystal-induced inflammation. Data obtained after cell pretreatment allow us to hypothesize that these polyphenols act on specific signaling pathways, preventing inflammation.