Apigenin inhibits immunostimulatory function of dendritic cells: Implication of immunotherapeutic adjuvant.
Apigenin, one of the most common flavonoids, has been shown to possess anti-inflammatory, anticarcinogenic, and free radical-scavenging properties. However, the influence of apigenin on the immunostimulatory effects and maturation of dendritic cells (DC) remains, for the most part, unknown. In this study, we have attempted to ascertain whether apigenin influences the expression of surface molecules, dextran uptake, cytokine production, and T-cell differentiation as well as the signaling pathways underlying these phenomena in murine bone marrow-derived DC. In the presence of apigenin, CD80, CD86, and major histocompatibility complex class I and II molecules, expressions on DC were significantly suppressed, and lipopolysaccharide (LPS)-induced interleukin (IL)-12 expression was impaired. The DC proved highly efficient at antigen capture, as evidenced by the observation of mannose receptor-mediated endocytosis in the presence of apigenin. The LPS-induced activation of mitogen-activated protein kinase, the nuclear translocation of its nuclear factor-kappaB p65 subunit, and the induction of the T-helper 1 response were all impaired in the presence of apigenin, whereas the cell-mediated immune response remained normal. These findings provide new insight into the immunopharmacological functions of apigenin and its effects on DC, and they may also prove useful in the development of adjuvant therapies for individuals suffering from acute or chronic DC-associated diseases.
Yoon
Man-Soo
MS
Department of Obstetrics and Gynecology, College of Medicine, Pusan National University, Pusan, Korea.
Lee
Jun Sik
JS
Choi
Byoung-Moon
BM
Jeong
Young-Il
YI
Lee
Chang-Min
CM
Park
Jong-Hoon
JH
Moon
Yuseok
Y
Sung
Si-Chan
SC
Lee
Sang Kwon
SK
Chang
Yun Hee
YH
Chung
Hae Young
HY
Park
Yeong-Min
YM
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D047310:Apigenin / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D004705:Endocytosis / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D016753:Interleukin-10; D018664:Interleukin-12; D047310:Apigenin; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases