Proteoglycan isolated from Phellinus linteus activates murine B lymphocytes via protein kinase C and protein tyrosine kinase.
Medicinal mushrooms are increasingly used to treat a wide variety of disease processes. Aqueous extract from the fruiting body or mycelia of Phellinus linteus has been reported to produce antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not been known. In the present study, we investigated whether proteoglycan (PL) isolated from P. linteus has an effect on the immunomodulatory activities of the murine splenic lymphocytes (MSLs). Treatment with PL caused a four-fold augmentation in [3H]thymidine incorporation compared to untreated control group in MSLs. Flow cytometric analysis indicated that the affected cell population was mainly CD19(+) cells, but not CD3(+) cells. These data suggested that the main target of PL was the B cells, but not T cells. PL also enhanced the expression of co-stimulatory molecules, CD80 and CD86, in murine B cells in a time-dependent manner. Accordingly, we investigated if intracellular [Ca(2+)] and reactive oxygen intermediates (ROI) were the principal downstream components that contributed to PL-induced activation, with respect to both increases of proliferation and induction of co-stimulatory molecules. However, PL has no influence on the [Ca(2+)] concentration and the ROI formation in murine B cells, whereas the genistein, protein tyrosine kinase (PTK) inhibitor or staurosporine, protein kinase C (PKC), blocked the proliferation and the induction of co-stimulatory molecules, CD80 and CD86, in B cells stimulated with PL. Taken together, these data suggest that PL is a biological response modifier that stimulates proliferation and expression of co-stimulatory molecules in B cells, probably by regulating PTK and PKC signaling pathways.
Kim
Gi-Young
GY
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, South Korea.
Park
Soon-Kew
SK
Lee
Min-Ki
MK
Lee
Sang-Hwa
SH
Oh
Yang-Hyo
YH
Kwak
Jong-Young
JY
Yoon
Sik
S
Lee
Jae-Dong
JD
Park
Yeong-Min
YM
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018941:Antigens, CD19 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000201:enzymology; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D001487:Basidiomycota / Q000737:chemistry*; D017252:CD3 Complex / Q000032:analysis; D020013:Calcium Signaling; D004261:DNA Replication / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011509:Proteoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology
D015703:Antigens, CD; D018941:Antigens, CD19; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017252:CD3 Complex; C497965:Cd86 protein, mouse; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D017382:Reactive Oxygen Species; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine