Abstract
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-κB 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-1β mechanism of matrine, as IL-1β is a major inflammatory cytokine, in porcine alveolar macrophages (PAMs) stimulated with 4 μg PRRSV 5′-untranslated region (UTR) RNA and 1 μg/mL LPS. After 5′UTR RNA and LPS co-stimulation of PAMs for 12 h, the expression of IL-1β, IL-6, IL-8 and TNF-α was significantly increased. The results also showed that co-stimulation induced the expression of MyD88, and activated the NF-κB signalling pathway and NLRP3 inflammasome. Furthermore, matrine treatment downregulated MyD88, NLRP3 and caspase-1 expression, inhibited ASC speck formation, suppressed IκBα phosphorylation, and interfered with the translocation of NF-κB 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-κB and the NLRP3 inflammasome. These findings lay the foundation for the exploration of the clinical application of matrine in PRRSV disease.
Highlights
IL-1β, a potent pro-inflammatory cytokine, predominantly produced by macrophages, monocytes and dendritic cells, that plays a central role in inflammatory and immune response regulation [1]
We suggested that matrine exhibits antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCV2) [23, 24]; the underlying antiviral mechanisms of matrine may be mediated by partly regulating the TLR3/TLR4/NF-κB/TNF-α pathway [23]
PRRSV 5′untranslated region (UTR) RNA and LPS co‐stimulation induced the secretion of inflammatory mediators The expression of inflammatory mediators, including IL-1β, IL-6, IL-8 and TNF-α, was measured in porcine alveolar macrophages (PAMs) treated with 5′UTR RNA alone, LPS alone or 5′UTR RNA and LPS in combination
Summary
IL-1β, a potent pro-inflammatory cytokine, predominantly produced by macrophages, monocytes and dendritic cells, that plays a central role in inflammatory and immune response regulation [1]. Active IL-1β production and secretion involves at least two signalling cascades [2,3,4]. The Toll-like receptors (TLRs) are a Infection by pathogens, including viruses, either up- or down-regulates cytokine levels. Previous studies have demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection induces. There are increasing numbers of studies on the mechanism of PRRSV initiating the host inflammatory response. Pathogenic PRRSV infection enhances IL-1β secretion that is dependent on the TLR4/MyD88/NF-κB/MAPK pathway and on the activation of NLRP3 inflammasome [12, 13]. Previous research has clearly demonstrated that PRRSV and bacterial lipopolysaccharide (LPS) act synergistically to multiply the inflammatory response of infected lungs or macrophages [17,18,19]
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