The role of tumor necrosis factor-α for interleukin-10 production by murine dendritic cells.
In the present study, we examined the role of tumor necrosis factor (TNF) in interleukin (IL)-10 production by dendritic cells (DCs) using bone-marrow derived DCs from wild type (WT) and TNF-α knockout (TNF-α(-/-)) mice. Toll-like receptor (TLR) stimulation induced substantial level of IL-10 production by WT DCs, but significantly low level of IL-10 production by TNF-α(-/-) DCs. In contrast, no significant difference was detected in IL-12 p40 production between WT and TNF-α(-/-) DCs. Addition of TNF-α during TLR stimulation recovered the impaired ability of TNF-α(-/-) DCs for IL-10 production. This recovery appeared to be associated with an activation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol 3-kinase/Akt following the TNF-α addition. Blocking these kinases significantly inhibited IL-10 production by TNF-α(-/-) DCs stimulated with TLR ligands plus TNF-α. Thus, TNF-α may be a key molecule to regulate the balance between anti-inflammatory versus inflammatory cytokine production in DCs.
Hirata
Noriyuki
N
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, West 7 North 15, Sapporo 060-0815, Japan.
Yanagawa
Yoshiki
Y
Ogura
Hisako
H
Satoh
Masashi
M
Noguchi
Masayuki
M
Matsumoto
Machiko
M
Togashi
Hiroko
H
Onoé
Kazunori
K
Iwabuchi
Kazuya
K
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D053762:Interleukin-12 Subunit p40; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D017346:Protein Serine-Threonine Kinases