Paeoniflorin suppresses IL-33 production by macrophages. (3rd May 2020)

• Record Type: Journal Article
• Authors: Li, Weihua; Tao, Wenting; Chen, Jiaojiao; Zhai, Yi; Yin, Nina; Wang, Zhigang
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 42:Number 3(2020)
• Page Start: 286
• Page End: 293
• Publication Date: 2020-05-03
• Subjects: Paeoniflorin -- interleukin-33 -- RAW264.7 macrophages -- NF-κB -- P38MAPK -- Ca2+ mobilization; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.1080/08923973.2020.1750628
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: Objective: 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. Methods: In vivo, IL-33 production in mice after lipopolysaccharide (LPS) injection together with PF application was detected by enzyme-linked immunosorbent assay (ELISA). In vitro, MTT, Real-time PCR, ELISA, Calcium (Ca 2+ ) imaging and Western blot were used to assess the cytotoxicity of PF, IL-33 expression at mRNA and protein levels, Ca 2+ 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. Results: 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. In vitro 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 2+ 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 2+ blocker (NiCl2 ) also curbed LPS-induced IL-33 production, respectively. Conclusions: PF suppresses IL-33 production by macrophages via inhibiting NF-κB and P38MAPK activation associated with the regulation of Ca 2+ mobilization.