ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced by the LPS signal in THP-1 cells.
LPS induces the production of inflammatory cytokines via the stimulation of Toll-like receptors. In this study, we demonstrated that a soluble secreted form of the ST2 gene product (ST2), a member of the interleukin-1 receptor family, suppressed the production of IL-6 in an LPS-stimulated human monocytic leukemia cell line, THP-1. Immunofluorescence confocal microscopy revealed the binding of ST2 to the surface of the THP-1 cells, in which ST2 led to decreased binding of nuclear factor-kappaB to the IL-6 promoter. Furthermore, the degradation of IkappaB in the cytoplasm after LPS stimulation was reduced by pretreatment with ST2. These results demonstrated that ST2 negatively regulates LPS-induced IL-6 production via the inhibition of IkappaB degradation in THP-1 cells.
Takezako
Naoki
N
Department of Biochemistry, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan.
Hayakawa
Morisada
M
Hayakawa
Hiroko
H
Aoki
Shinsuke
S
Yanagisawa
Ken
K
Endo
Hitoshi
H
Tominaga
Shin-ichi
S
D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D007375:Interleukin-1 / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007763:Lac Operon; D008070:Lipopolysaccharides / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D009000:Monocytes / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016622:Silver Staining; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018076:DNA, Complementary; D020672:I-kappa B Proteins; C079241:IL1RL1 protein, human; D007375:Interleukin-1; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C000606204:NFKBIA protein, human; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha