Involvement of interleukin-1 receptor-associated kinase (IRAK)-M in toll-like receptor (TLR) 7-mediated tolerance in RAW 264.7 macrophage-like cells.
The effect of toll-like receptor (TLR) 7 ligand pretreatment on the production of tumor necrosis factor (TNF)-alpha in response to TLR7 or TLR2 ligand was examined in order to establish a new TLR-mediated tolerance. RAW 264.7 macrophage-like cells were treated with imiquimod R837 as a TLR7 ligand for 18h, washed and incubated in fresh culture medium 6h. The second challenge with imiquimod R837 as a TLR7 ligand or Pam3CysSK4 as a TLR2 ligand resulted in reduced TNF-alpha production in TLR7 ligand-pretreated cells. There was impaired activation of NF-kappaB, p38 and stress-activated protein kinase (SAPK) in the tolerant cells. The expression of IRAK-M as a negative regulator of TLR signaling was markedly augmented in the tolerant cells while the interleukin-1 receptor-associated kinase (IRAK)-1 functioned normally. The involvement of IRAK-M in the TLR7-mediated tolerance is discussed.
Hassan
Ferdaus
F
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Yazako, Nagakute, Japan.
Islam
Shamima
S
Tumurkhuu
Gantsetseg
G
Dagvadorj
Jargalsaikhan
J
Naiki
Yoshikazu
Y
Komatsu
Takayuki
T
Koide
Naoki
N
Yoshida
Tomoaki
T
Yokochi
Takashi
T
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D000077271:Imiquimod; D007108:Immune Tolerance / Q000502:physiology*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000634:Aminoquinolines; D017931:DNA Primers; D008024:Ligands; D055666:Lipopeptides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C508075:Pam(3)CSK(4) peptide; D034741:RNA, Small Interfering; C493486:Tlr2 protein, mouse; C477038:Tlr7 protein, mouse; D051195:Toll-Like Receptor 2; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; C507772:Irak3 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D000077271:Imiquimod