LAUSR

Background: The activation of NLRP3 inflammasome is involved in the aggravated inflammatory response of COPD exacerbations. However, there is a lack of treatment options targeting this specific pathway while andrographolide is shown to benefit certain inflammatory diseases by reducing IL-1β production. Objective: This study aims to examine the effect of andrographolide on the NLRP3 inflammasome pathway activation in COPD. Methods: THP-1 monocytes were stimulated with PMA to induce monocyte-to-macrophage differentiation. THP-1 macrophages were treated with andrographolide on concentrations of 10, 20 and 40 µmol/L for 1h, followed by stimulation of LPS for 24h and ATP for 1h to activate NLRP3 inflammasome. Positive and negative control were established by interfering cells with NLRP3 specific siRNA and DMSO respectively. PBMCs were isolated from COPD patients’ peripheral blood and incubated with GM-CSF for macrophage differentiation. Macrophages were treated with andrographolide and stimulated with LPS+ATP as previously described. Cell culture supernatants were collected for IL-1β assay, and cells were harvested for NRLP3, ASC, Caspase-1 and IL-1β gene and protein assays by qPCR and Western-blot. Results: Andrographolide significantly downregulated NLRP3, Caspase-1 and IL-1β gene expression and protein levels in THP-1 macrophages. In COPD, 20 and 40 µmol/L of andrographolide significantly inhibited NLRP3 inflammasome activation manifested by the decreased protein levels of NLRP3, Caspase-1 and IL-1β production in monocytes-derived macrophages. Conclusion: Natural product andrographolide inhibited the NLRP3 inflammasome activation in COPD and might be a potential strategy to target COPD excerbations.