Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets.
Curcumin has been shown to exhibit anti-inflammatory, antimutagenic, and anticarcinogenic activities. However, the effect of curcumin on the maturation and immunostimulatory function of dendritic cells (DC) largely remains unknown. In this study, we examined whether curcumin can influence surface molecule expression, cytokine production, and their underlying signaling pathways in murine bone marrow-derived DC. DC were derived from murine bone marrow cells and used as immature or LPS-stimulated mature cells. The DC were tested for surface molecule expression, cytokine production, dextran uptake, the capacity to induce T cell differentiation, and their underlying signaling pathways. Curcumin significantly suppressed CD80, CD86, and MHC class II expression, but not MHC class I expression, in the DC. The DC also exhibited impaired IL-12 expression and proinflammatory cytokine production (IL-1beta, IL-6, and TNF-alpha). The curcumin-treated DC were highly efficient at Ag capture, via mannose receptor-mediated endocytosis. Curcumin inhibited LPS-induced MAPK activation and the translocation of NF-kappaB p65. In addition, the curcumin-treated DC showed an impaired induction of Th1 responses and a normal cell-mediated immune response. These novel findings provide new insight into the immunopharmacological role of curcumin in impacting on the DC. These novel findings open perspectives for the understanding of the immunopharmacological role of curcumin and therapeutic adjuvants for DC-related acute and chronic diseases.
Kim
Gi-Young
GY
Department of Microbiology and Immunology, and National Research Lab of Dendritic Cell Differentiation & Regulation and Medical Research Institute, Pusan National University College of Medicine, Pusan, South Korea.
Kim
Ki-Hyung
KH
Lee
Soong-Hwan
SH
Yoon
Man-Soo
MS
Lee
Hee-Jeong
HJ
Moon
Dong-Oh
DO
Lee
Chang-Min
CM
Ahn
Soon-Cheol
SC
Park
Young Chul
YC
Park
Yeong-Min
YM
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D016753:Interleukin-10 / Q000502:physiology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051996:Transcription Factor RelA; D016753:Interleukin-10; D018664:Interleukin-12; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin