Int Immunol 2005,
PMID: 16263754
Kim, Jung Mogg; Kim, Nam In; Oh, Yu-Kyoung; Kim, Young-Jeon; Youn, Jeehee; Ahn, Myung-Ju
To elucidate the role of Toll-like receptor 9 (TLR9) activation along with the intracellular signaling pathways triggered by CpG DNA in CD34+ cells, we investigated whether synthetic oligodeoxynucleotides (ODNs), containing unmethylated CpG motifs, could induce IL-8 expression in CD34+ cells through mitogen-activated protein kinase (MAPK) or nuclear factor-kappaB (NF-kappaB) pathway. We demonstrated evidence for the first time that CD34+ cells constitutively expressed TLR9. Exposure of the cells to CpG ODN resulted in a time- and dose-dependent increase of IL-8 expression, and activation of phosphorylated ERK1/2 and phosphorylated p38. In addition, CpG ODN stimulated AP-1, but not NF-kappaB, signals. Moreover, inhibitors of MAPK (U0126 and SB203580) significantly reduced the IL-8 production, while the inhibition of NF-kappaB (pyrrolidinedithiocarbamate and retrovirus containing dominant-negative IkappaB alpha plasmid) did not affect the IL-8 expression increased by CpG ODN. Moreover, co-stimulation with LPS and CpG synergistically up-regulates IL-8 in CD34+ cells. These results suggest that CpG DNA, acting on TLR9, activates CD34+ cells to express IL-8 through MAPK-dependent and NF-kappaB-independent pathways.
Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed
Text Mining Data
mitogen activated protein kinase → IL-8: "
To elucidate the role of Toll-like receptor 9 (TLR9) activation along with the intracellular signaling pathways triggered by CpG DNA in CD34+ cells, we investigated whether synthetic oligodeoxynucleotides ( ODNs ), containing unmethylated CpG motifs, could
induce IL-8 expression in CD34+ cells through
mitogen activated protein kinase ( MAPK ) or nuclear factor-kappaB (NF-kappaB) pathway
"
p38 → IL-8: "
Exposure of the cells to CpG ODN resulted in a time- and dose dependent increase of IL-8 expression, and activation of phosphorylated ERK1/2 and phosphorylated p38
"
ERK1/2 → IL-8: "
Exposure of the cells to CpG ODN resulted in a time- and dose dependent increase of IL-8 expression, and activation of phosphorylated ERK1/2 and phosphorylated p38
"
IL-8 ⊣ MAPK: "
Moreover, inhibitors of MAPK ( U0126 and SB203580 ) significantly reduced the IL-8 production, while the inhibition of NF-kappaB ( pyrrolidinedithiocarbamate and retrovirus containing dominant negative IkappaB alpha plasmid ) did not affect the IL-8 expression increased by CpG ODN
"
NF-kappaB ⊣ MAPK: "
Moreover, inhibitors of MAPK ( U0126 and SB203580 ) significantly reduced the IL-8 production, while the inhibition of NF-kappaB ( pyrrolidinedithiocarbamate and retrovirus containing dominant negative IkappaB alpha plasmid ) did not affect the IL-8 expression increased by CpG ODN
"
IL-8 — NF-kappaB: "
Moreover, inhibitors of MAPK ( U0126 and SB203580 ) significantly reduced the IL-8 production, while the inhibition of NF-kappaB ( pyrrolidinedithiocarbamate and retrovirus containing dominant negative IkappaB alpha plasmid ) did not affect the IL-8 expression increased by CpG ODN
"
Manually curated Databases
No curated data.