Inhibition of phenotypic and functional maturation of dendritic cells by manassantin a.
Manassantin A (MSA) inhibits nitric oxide production by macrophages through the inhibition of NF-kappaB activation, but the effect of MSA on dendritic cells has not been elucidated yet. Here we investigated the inhibitory effects of MSA on immune functions of dendritic cells (DCs). MSA inhibited lipopolysaccharide (LPS)-induced phenotypic maturation of DCs, which was proved by the decreased expression of CD40, CD80, CD86, MHC-I, and MHC-II. MSA also inhibited functional maturation of DCs, that is, decreased the gene expression of IL-12, IL-1beta, TNF-alpha, and IFN-alpha/beta; enhanced antigen capture capacity of DCs; and impaired induction of allogenic T cell activation. As a mechanism of action, MSA inhibited LPS-induced activation of NF-kappaB, ERK, p38, and JNK, which played pivotal roles in toll-like receptor 4-mediated DC maturation. Collectively, these results suggested that MSA might be used for the treatment of DC-related immune diseases.
College of Pharmacy, Chungbuk National University, Chungbuk, Korea.
Jee Youn
JY
Kim
Jong Soon
JS
Kang
Hwan Mook
HM
Kim
Young Kook
YK
Kim
Hong Kyung
HK
Lee
Sukgil
S
Song
Jin Tae
JT
Hong
Youngsoo
Y
Kim
Sang-Bae
SB
Han
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003713:Dendritic Cells / Q000187:drug effects*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000187:drug effects; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics
D014150:Antipsychotic Agents; D007376:Interleukin-2; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma; C054895:manassantin A; D020928:Mitogen-Activated Protein Kinases