Low-dose lipopolysaccharide modifies the production of IL-12 by dendritic cells in response to various cytokines.
Dendritic cell (DC) activation is triggered by cytokines, including tumor necrosis factor (TNF)-alpha, and microbe components, including lipopolysaccharide (LPS). During the initial stage of infection, the microbe components appear to be present at low concentration. To determine the role of low-dose microbe-components in DC activation during the initial stage of infection, we examined the effects of low-dose LPS on cytokine-induced maturation and function of DCs. Low-dose LPS (1 ng/ml) treatment of DCs had only additive effects on the expression of CD86 and major histocompatibility complex class II induced by various cytokines, including interleukin (IL)-1beta, TNF-alpha and interferon (IFN)-gamma. IL-1beta alone significantly induced IL-12 production in DCs, whereas TNF-alpha or IFN-gamma induced modest levels of IL-12 production. When low-dose LPS (1 ng/ml), which only slightly induced IL-12 production, was added to the culture, only an additive effect was seen on IL-1beta-induced IL-12 production. In contrast, low-dose LPS synergistically enhanced TNF-alpha- or IFN-gamma-induced IL-12 production. SB203580, a specific inhibitor of p38 MAPK, markedly inhibited TNF-alpha- or IFN-gamma-induced IL-12-production either in the absence or presence of LPS, but showed only modest effects on IL-beta-induced IL-12-production. These findings suggest that the p38 MAPK pathway is essential for the synergistic IL-12 production induced by TNF-alpha- or IFN-gamma in combination with low-dose LPS in DC.
Saito
Yusuke
Y
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan.
Yanagawa
Yoshiki
Y
Kikuchi
Kazuhiro
K
Iijima
Norifumi
N
Iwabuchi
Kazuya
K
Onoé
Kazunori
K
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
D016207:Cytokines; D008070:Lipopolysaccharides; D018664:Interleukin-12