Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4+ T cells by modulating T cell receptor signaling.
The protein-bound polysaccharide isolated from basidiomycetes (PSK), a biological response modifier, has been used as immunotherapeutic agent for the treatment of cancers. It has been demonstrated previously that PSK activates various types of immune cells in vitro, and orally administrated PSK activates anti-tumor CD4+ T cell response in mesenteric lymph nodes (MLNs). The detailed mechanism of action of PSK, however, has not been elucidated yet. The objective of the present study was to clarify the molecular mechanism of immunopotentiating effects of PSK using primary culture of the MLN CD4+ T cells. T cell receptor (TCR) stimulation-induced interleukin-2 production from MLN CD4+ T cells was significantly augmented by PSK in a concentration-dependent manner, and the augmentation was reflected at mRNA level. Furthermore, PSK augmented transcriptional activities of nuclear factor of activated T cells and activator protein 1, and phosphorylation of extracellular signal-regulated kinase 1/2 and linker for activation of T cells induced by TCR stimulation, whereas PSK had no influences without TCR stimulation. Collectively, the results indicate that PSK augments activation of MLN CD4+ T cells, probably by modulating the TCR signaling, and provide important knowledge for the elucidation of the true target molecule(s) of PSK.
Asai
Hirobumi
H
Biomedical Research Laboratories, Kureha Corporation, 3-26-2 Hyakunin-cho, Shinjuku-ku, Tokyo 169-8503, Japan. asaih@kureha.co.jp
Iijima
Hiroko
H
Matsunaga
Kenichi
K
Oguchi
Yoshiharu
Y
Katsuno
Hidetoshi
H
Maeda
Koutaro
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D007376:Interleukin-2 / Q000096:biosynthesis*; D008156:Luciferases / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology*; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D050778:NFATC Transcription Factors / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D011509:Proteoglycans; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; C010770:polysaccharide-K; D008156:Luciferases