Plant-derived small molecule albaconol suppresses LPS-triggered proinflammatory cytokine production and antigen presentation of dendritic cells by impairing NF-kappaB activation.
Dendritic cells (DCs) play crucial roles in linking innate immunity and adaptive immunity, thus being regarded as one of the important targets of immunosuppressant. Natural small molecule products isolated from plants, such as fungal metabolites, have been shown to be effective in the treatment of cancer, inflammation and autoimmune diseases. Albaconol is a new kind of prenylated resorcinols isolated from the fruiting bodies of the inedible mushroom Albatrellus confluens, and has been shown to inhibit tumor cell growth. Considering that most of small molecule compounds with antitumor activity always exert immunosuppressive effect, so we wonder whether albaconol could inhibit maturation and antigen presentation of DCs, thus acting as immunosuppressant. Here we demonstrate that albaconol significantly inhibits LPS-induced production of proinflammatory cytokines TNF-alpha, IL-6, IL-1beta, and expression of MHC-II and co-stimulatory molecules by DCs. Furthermore, albaconol markedly inhibits T cell-stimulating capacity of DCs and DCs-initiated antigen-specific T cell response, indicating albaconol can inhibit phenotypic and functional maturation of DCs. Inhibition of LPS-induced NF-kappaB activation may contribute to the above immunosuppressive or anti-inflammatory activities of albaconol. Therefore, our results suggest that natural small molecule albaconol may be a potential immunosuppressive and anti-inflammatory agent through suppressing DCs function via impairment of NF-kappaB activation.
Liu
Qiuyan
Q
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, PR China.
Shu
Xiaoli
X
Sun
Anna
A
Sun
Qiaoling
Q
Zhang
Chaoxiong
C
An
Huazhang
H
Liu
Jikai
J
Cao
Xuetao
X
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007165:Immunosuppression Therapy; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010636:Phenols; C478999:albaconol; D010047:Ovalbumin