Xiaojuan Xu1, Michiko Yasuda, Masashi Mizuno, Hitoshi Ashida. 1. Department of Agrobioscience, Applied Chemistry in Bioscience Division, Graduate School of Agricultural Science, Kobe University 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
Abstract
BACKGROUND: β-Glucans obtained from fungi, such as baker's yeast (Saccharomyces cerevisiae)-derived β-glucan (BBG), potently activate macrophages through nuclear factor κB (NFκB) translocation and activation of its signaling pathways. The mechanisms by which β-glucans activate these signaling pathways differ from that of lipopolysaccharide (LPS). However, the effects of β-glucans on LPS-induced inflammatory responses are poorly understood. Here, we examined the effects of BBG on LPS-induced inflammatory responses in RAW264.7 mouse macrophages. METHODS: We explored the actions of BBG in RAW264.7 macrophages. RESULTS: BBG inhibited LPS-stimulated nitric oxide (NO) production in RAW264.7 macrophages by 35-70% at concentrations of 120-200μg/ml. BBG also suppressed mRNA and protein expression of LPS-induced inducible NO synthase (iNOS) and mitogen-activated protein kinase phosphorylation, but not NFκB activation. By contrast, a neutralizing antibody against dectin-1, a β-glucan receptor, did not affect BBG-mediated inhibition of NO production. Meanwhile, BBG suppressed Pam3CSK-induced NO production. Moreover, BBG suppressed LPS-induced production of pro-and anti-inflammatory cytokines, including interleukin (IL)-1α, IL-1ra, and IL-27. CONCLUSIONS: Our results indicate that BBG is a powerful inhibitor of LPS-induced NO production by downregulating iNOS expression. The mechanism involves inactivation of mitogen-activated protein kinase and TLR2 pathway, but is independent of dectin-1. GENERAL SIGNIFICANCE: BBG might be useful as a novel agent for the chemoprevention of inflammatory diseases.
BACKGROUND: β-Glucans obtained from fungi, such as baker's yeast (Saccharomyces cerevisiae)-derived β-glucan (BBG), potently activate macrophages through nuclear factor κB (NFκB) translocation and activation of its signaling pathways. The mechanisms by which β-glucans activate these signaling pathways differ from that of lipopolysaccharide (LPS). However, the effects of β-glucans on LPS-induced inflammatory responses are poorly understood. Here, we examined the effects of BBG on LPS-induced inflammatory responses in RAW264.7 mouse macrophages. METHODS: We explored the actions of BBG in RAW264.7 macrophages. RESULTS:BBG inhibited LPS-stimulated nitric oxide (NO) production in RAW264.7 macrophages by 35-70% at concentrations of 120-200μg/ml. BBG also suppressed mRNA and protein expression of LPS-induced inducible NO synthase (iNOS) and mitogen-activated protein kinase phosphorylation, but not NFκB activation. By contrast, a neutralizing antibody against dectin-1, a β-glucan receptor, did not affect BBG-mediated inhibition of NO production. Meanwhile, BBG suppressed Pam3CSK-induced NO production. Moreover, BBG suppressed LPS-induced production of pro-and anti-inflammatory cytokines, including interleukin (IL)-1α, IL-1ra, and IL-27. CONCLUSIONS: Our results indicate that BBG is a powerful inhibitor of LPS-induced NO production by downregulating iNOS expression. The mechanism involves inactivation of mitogen-activated protein kinase and TLR2 pathway, but is independent of dectin-1. GENERAL SIGNIFICANCE: BBG might be useful as a novel agent for the chemoprevention of inflammatory diseases.
Authors: Sanne P Smeekens; Mark S Gresnigt; Katharina L Becker; Shih-Chin Cheng; Stejara A Netea; Liesbeth Jacobs; Trees Jansen; Frank L van de Veerdonk; David L Williams; Leo A B Joosten; Charles A Dinarello; Mihai G Netea Journal: Cytokine Date: 2014-11-20 Impact factor: 3.861