Proteoglycan isolated from Phellinus linteus inhibits tumor growth through mechanisms leading to an activation of CD11c+CD8+ DC and type I helper T cell-dominant immune state.
Dendritic cells (DC) are known to not only induce the activation of T cells, but are also associated with the polarization of T cells. This study investigated whether or not proteoglycan (PG) isolated from Phellinus linteus induces the phenotypic and functional maturation of CD11c+ DC in vitro and in vivo. PG was found to induce the phenotypic and functional maturation of bone marrow-derived DC via Toll-like receptors (TLR) 2 and 4 in vitro. Administration of PG in vivo strongly inhibited the MCA-102 tumor growth and increase in vivo. The ratio of CD8+ DC to CD8- DC increased, and PG enhanced IL-12 and IFN-gamma production, and expression of surface molecules including major histocompatibility complexes (MHC) classes I, MHC II, CD80, and CD86 in MCA-102-challenged mice. PG also caused a marked increase in the production of Th (helper T cells)-1 cytokine (IFN-gamma) and a decrease in the production of Th-2 cytokine (IL-4) by splenic cells and inguinal lymph node cells in MCA-102 tumor-bearing mice. Furthermore, PG stimulated the proliferation of CD4+ and CD8+ T cells. In addition, a combination of PG and tumor lysate-pulsed DC inhibited completely the growth of MCA-102 cells in tumor-bearing mice. These results indicate that the administration of PG inhibited the tumor growth through a mechanism leading to a Th-1 dominant immune state and the activation of CD11cCD8+ DC.
Kim
Gi-Young
GY
Department of Microbiology and Immunology, and Medical Research Institute, Pusan National University College of Medicine, Ami-dong 1-10, Seo-gu, Pusan 602-739, Republic of Korea.
Oh
Won-Kyo
WK
Shin
Byung-Cheul
BC
Shin
Yong-Il
YI
Park
Young-Chul
YC
Ahn
Soon-Cheol
SC
Lee
Jae-Dong
JD
Bae
Yoe-Sik
YS
Kwak
Jong-Young
JY
Park
Yeong-Min
YM
D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology*
D000970:Antineoplastic Agents; D011509:Proteoglycans