Protein-bound polysaccharide isolated from basidiomycetes inhibits endotoxin-induced activation by blocking lipopolysaccharide-binding protein and CD14 functions.
The protein-bound polysaccharide isolated from basidiomycetes (PSK) is a biological response modifier capable of exhibiting various biological activities, such as antitumor and antimicrobial effects. In the present study, we found that PSK suppressed interleukin (IL)-6 production in murine peritoneal macrophages stimulated with endotoxic lipopolysaccharide (LPS) and its synthetic lipid A (compound 506). Nitric oxide production and p38 mitogen-associated protein kinase phosphorylation induced in a murine macrophage cell line, J774-A1, by LPS and compound 506 were also inhibited by PSK. Further, PSK distinctly suppressed nuclear factor-kappaB activation in Ba/F3 cells expressing mouse Toll-like receptor 4 and MD-2, following stimulation with LPS and compound 506, however, not with Taxol. These PSK-induced inhibitory activities were caused by inhibition of the physical associations of LPS with LPS-binding protein (LBP) and CD14. PSK also protected mice from LPS-induced lethality, presumably by down-regulating IL-6 and tumor necrosis factor-alpha concentrations in serum. These findings indicate that PSK, which also has an ability to regulate LBP/CD14 functions, may be useful for clinical control of endotoxic sepsis.
Asai
Yasuyuki
Y
Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan.
Takaori
Kyoichi
K
Yamamoto
Tsuyoshi
T
Ogawa
Tomohiko
T
D000209:Acute-Phase Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D000818:Animals; D000992:Antitoxins / Q000494:pharmacology*; D001487:Basidiomycota / Q000737:chemistry*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000096:biosynthesis; D008050:Lipid A / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000032:analysis; D009569:Nitric Oxide / Q000096:biosynthesis; D011509:Proteoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000992:Antitoxins; D002352:Carrier Proteins; D015850:Interleukin-6; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009569:Nitric Oxide; D011509:Proteoglycans; D011971:Receptors, Immunologic; D048051:p38 Mitogen-Activated Protein Kinases; D000099231:Lipopolysaccharide-Binding Protein; C010770:polysaccharide-K