Levamisole enhances immune response by affecting the activation and maturation of human monocyte-derived dendritic cells.
Levamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent. Current studies have been focused upon its effect on immune response and on cancer treatment. We examined the molecular mechanisms of levamisole in the activation and maturation of human monocyte-derived dendritic cells (DC) and human T cells. Treatment of DC with levamisole increased the presentation of CD80, CD86, CD83 and human leucocyte antigen D-related (HLA-DR) molecules on the cell membrane, as well as the production of interleukin (IL)-12 p40 and IL-10. Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune response by inducing interferon-gamma secretion. Neutralization with antibodies against Toll-like receptor (TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10, suggesting a vital role for TLR-2 in signalling DC upon incubation with levamisole. The inhibition of nuclear factor-kappaB, extracellular signal-regulated kinases 1/2 or c-Jun N-terminal kinases pathways also prevented the effects of levamisole on DC in producing IL-12 p40 or IL-10. Taken together, levamisole could enhance immune response towards T helper 1 development through the activation of dendritic cells or T cell aspects.
Chen
L-Y
LY
Department of Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Lin
Y-L
YL
Chiang
B-L
BL
D000871:Anthelmintics / Q000627:therapeutic use*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D007978:Levamisole / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D020935:MAP Kinase Signaling System / Q000187:drug effects; D013268:Stimulation, Chemical; D018417:Th1 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology
D000871:Anthelmintics; D006684:HLA-DR Antigens; D053762:Interleukin-12 Subunit p40; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D007978:Levamisole; D007371:Interferon-gamma