Paeoniflorin suppresses IL-33 production by macrophages.

Interleukin (IL)-33 has been attracting more and more attention as a new member of theIL-1 cytokine family in recent years. However, the underlying mechanisms referred to the regulation of endogenous IL-33 production are not fully illustrated. Paeoniflorin (PF) has been reported to possess multiple pharmacological activities, including anti-inflammation and anti-allergy. In this study, we aimed to investigate the effect of PF on IL-33 production by macrophages and explore the underlying mechanisms. , IL-33 production in mice after lipopolysaccharide (LPS) injection together with PF application was detected by enzyme-linked immunosorbent assay (ELISA). , MTT, Real-time PCR, ELISA, Calcium (Ca) imaging and Western blot were used to assess the cytotoxicity of PF, IL-33 expression at mRNA and protein levels, Ca influx, protein kinase C (PKC) activity, nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) activation in LPS-stimulated RAW264.7 macrophages with PF administration. Our results indicated that PF (5 and 25 mg/kg) significantly reduced the production of TNF-a, IL-1β, and IL-33 in the peritoneal exudate of LPS-treated mice. assay, upregulation of PF concentration (≥ 20 μM) showed an increased cytotoxicity in RAW264.7 cells during the 24-h cell culture. PF (10 μM) inhibited IL-33 production, Ca influx, PKC activity, NF-κB (p65) activation, and P38MAPK phosphorylation in LPS-treated macrophages. Notably, NF-κB inhibitor (BAY 11-7085), P38MAPK inhibitor (SB203580), and Ca blocker (NiCl) also curbed LPS-induced IL-33 production, respectively. PF suppresses IL-33 production by macrophages inhibiting NF-κB and P38MAPK activation associated with the regulation of Ca mobilization.