Matrine inhibits IL-1β secretion in primary porcine alveolar macrophages through the MyD88/NF-κB pathway and NLRP3 inflammasome

Our previous studies demonstrated that matrine directly acts on the replication process of porcine reproductive and respiratory syndrome virus (PRRSV). Matrine inhibits viral replication and is also associated with the NF-kappa B signalling pathway. These results suggest that matrine has antiviral and anti-inflammatory effects. However, the specific anti-inflammatory mechanism of matrine is still unclear. In this study, we investigated the anti-IL-1 beta mechanism of matrine, as IL-1 beta is a major inflammatory cytokine, in porcine alveolar macrophages (PAMs) stimulated with 4 mu g PRRSV 5 '-untranslated region (UTR) RNA and 1 mu g/mL LPS. After 5 ' UTR RNA and LPS co-stimulation of PAMs for 12h, the expression of IL-1 beta, IL-6, IL-8 and TNF-alpha was significantly increased. The results also showed that co-stimulation induced the expression of MyD88, and activated the NF-kappa B signalling pathway and NLRP3 inflammasome. Furthermore, matrine treatment downregulated MyD88, NLRP3 and caspase-1 expression, inhibited ASC speck formation, suppressed I kappa B alpha phosphorylation, and interfered with the translocation of NF-kappa B from the cytoplasm to the nucleus. These results suggest that matrine plays an important role in PAMs co-stimulated with PRRSV 5 ' UTR RNA and LPS via its effect on NF-kappa B and the NLRP3 inflammasome. These findings lay the foundation for the exploration of the clinical application of matrine in PRRSV disease.