Proteoglycan isolated from Phellinus linteus induces toll-like receptors 2- and 4-mediated maturation of murine dendritic cells via activation of ERK, p38, and NF-kappaB.
Mushroom polysaccharides are increasingly being utilized to treat a wide variety of diseases. Phellinus linteus proteoglycan (PL) has been reported to have anti-tumor and immunomodulatory properties. However, the cellular and molecular mechanism underlying its therapeutic effect is poorly understood. In this study, we investigated whether PL induces the phenotypic and functional maturation of murine bone marrow-derived dendritic cells (DC) and the possibility that Toll-like receptors (TLRs), which are known to be involved in immune-related responses, may be the receptor(s) of PL. The expression of surface molecules, including major histocompatibility complex (MHC) class II and CD86, increased on DC that were stimulated in a dose-dependent manner with PL, in comparison with unstimulated DC. Furthermore, PL increases the production of IL-12 by DC, as well as the IL-2 secretion and proliferation of allogeneic T cells. In addition, the activities of PL on DC were significantly reduced by treating the cells with anti-TLR2 or anti-TLR4 antibody (Ab) prior to PL, suggesting that both of them are possible receptors of PL. Also, maturation of DC by PL was able to directly activate mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38, and the nuclear transcription factor NF-kappaB p65. Also, the pretreatment of DC with inhibitors of NF-kappaB p65, and ERK and p38 MAPK signal pathways inhibited PL-induced up-regulation of surface molecules, such as MHC class II and CD86, and IL-12 production. Our results demonstrated that PL stimulation could induce the phenotypic and functional maturation of DC via TLR2 and/or TLR4 mediated-NF-kappaB, ERK and p38 MAPK signal pathways.
Kim
Gi-Young
GY
Deparmtment of Microbiology, Pusan National University College of Medicine, South Korea.
Han
Myung-Geum
MG
Song
Yung-Sun
YS
Shin
Byung-Cheul
BC
Shin
Yong-Il
YI
Lee
Hee-Jeong
HJ
Moon
Dong-Oh
DO
Lee
Chang-Min
CM
Kwak
Jong-Young
JY
Bae
Yoe-Sik
YS
Lee
Jae-Dong
JD
Park
Yeong-Min
YM
D000364:Agaricus; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D004705:Endocytosis; D004789:Enzyme Activation; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000819:agonists*; D010641:Phenotype; D021381:Protein Transport; D011509:Proteoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; D011509:Proteoglycans; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018664:Interleukin-12; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases