Stimulation of macrophages with the β-glucan produced by aureobasidium pullulans promotes the secretion of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)

• Published in: PloS one 2015-04, Vol.10 (4), p.e0124809-e0124809
• Main Authors: Kawata, Koji, Iwai, Atsushi, Muramatsu, Daisuke, Aoki, Shiho, Uchiyama, Hirofumi, Okabe, Mitsuyasu, Hayakawa, Sumio, Takaoka, Akinori, Miyazaki, Tadaaki
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antitumor agents; Apoptosis; Apoptosis - drug effects; Ascomycota - growth & development; Ascomycota - metabolism; Aureobasidium pullulans; Bacteria; beta-Glucans - pharmacology; Caspases - metabolism; Cell activation; Cells, Cultured; Chains; FasL protein; Gene expression; Glucan; Glucans; Humans; Macrophages; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Mice; Necrosis; Polysaccharides, Bacterial - pharmacology; Stimulation; TNF-Related Apoptosis-Inducing Ligand - metabolism; TRAIL protein; Transformed cells; Tumor cells; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-α; β-Glucan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124809

A β-glucan produced by Aureobasidium pullulans (AP-PG) is consisting of a β-(1,3)-linked main chain with β-(1,6)-linked glucose side residues. Various β-glucans consisting of β-(1,3)-linked main chain including AP-PG are believed to exhibit anti-tumor activities, and actually, anti-tumor activities of AP-PG in mice have been demonstrated. In this study, we demonstrate that stimulation with AP-PG induces TRAIL expression in mouse and human macrophage-like cell lines. TRAIL is known to be a cytokine which specifically induces apoptosis in transformed cells, but not in untransformed cells. The expression of TRAIL mRNA after stimulation with AP-PG was increased in RAW264.7 cells, Mono Mac 6 cells, and macrophage-differentiated THP-1 cells. The mRNA expression of TNF-α and FasL is only weakly increased after stimulation with AP-PG. The induction activity of TRAIL by curdlan, a bacterial β-glucan, was very similar to that by AP-PG in RAW264.7 cells, but weaker in macrophage-differentiated THP-1 cells. Activation of caspases was found in HeLa cells after treatment with the supernatant of cultured medium from AP-PG-stimulated Mono Mac 6 cells, and was inhibited by the anti-TRAIL neutralizing antibody. These findings suggest that the stimulation with AP-PG effectively induces TRAIL in macrophages, and that it may be related to apoptosis induction of tumor cells.