Berberine (BBR) possesses many pharmacological characteristics including anti-inflammation, anti-allergy, anti-angiogenesis and anti-tumor. However, the effects and mechanisms of BBR on IL-33-induced mast cell inflammatory responses are kept unknown. To investigate these, rat peritoneal mast cells (RPMCs) were isolated from the peritoneal cavity and cultured with BBR treatment in combination IL-33 stimulation. Firstly, cytotoxic effect of BBR on RPMCs was detected by MTT assay. Then, IL-33-induced cytokine production and the expression of ST2 receptor, were evaluated by ELISA and real-time PCR, respectively. In addition, NF-κB and MAPK signaling involved in IL-33-mediated mast cell activation were assessed by Western blot, which also was confirmed using the signal transduction inhibitors. Simultaneously, the effect of BBR on IL-33-activated enhancement of IgE-mediated mast cell responses was analyzed. Lastly, SD rats were used to explore the effect of BBR on IL-33-induced inflammation in vivo. BBR treatment significantly reduced IL-33-stimulated cytokine production in RPMCs, such as IL-6, TNF-α, IL-13 and MCP-1, but had little effect in ST2 expression. BBR modulated IL-33 signaling via suppressing IL-33-induced NF-ΚB transcription and p38 phosphorylation, but not ERK and JNK. Additionally, BBR also hampered the combined effects of IL-33 and IgE-mediated mast cell activation. Decreased cytokine production followed BBR treatment in vitro was consistent with that in vivo, where BBR injection i.p. into rats obviously inhibited IL-33-induced plasma cytokine levels. These findings demonstrated that BBR suppressed IL-33-mediated inflammation in mast cells by inactivating NF-κB and p38 signaling, suggesting its potential application for the treatment of allergic inflammation.
Keywords: Berberine; IL-33; Inflammation; Mast cells; NF-κB; p38 signaling.
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