Inhibition of Lipopolysaccharide-stimulated Inflammatory Cytokine Production by LY303511 in Human Macrophagic THP-1 Cells
International Journal of Oral Biology
;
: 117-121, 2017.
Article
in English
| WPRIM
| ID: wpr-201473
ABSTRACT
We have previously shown that the specific phosphatidylinositol 3-kinase inhibitor LY294002 (LY29), and its inactive analog LY303511 (LY30), inhibit a monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells; these results suggest the potential of LY30 as an anti-inflammatory drug. In this study, we determined the effects of LY30 on the production of various inflammatory cytokines in human macrophagic THP-1 cells which were stimulated with lipopolysaccharide (LPS). LY30 selectively suppressed the mRNA expression of IL-12 p40, TNF-α, and MCP-1 without affecting the expression of IL-1α, IL-6, and IL-8. Inhibition of the production of IL-12 and TNF-α by LY30 was also demonstrated using ELISA assays. In order to elucidate the mechanisms of the action of LY30, we examined the role played by the mitogen-activated protein kinases and the key transcription factors, AP-1 and NF-κB in LPS-stimulated THP-1 cells. The results revealed that LY30 inhibited LPS-induced activation of ERK, but not p38 or JNK. Furthermore, the AP-1 DNA binding activity was suppressed by LY30 based upon the dosage, whereas NF-κB DNA binding was not affected. These results suggest that LY30 selectively inhibits cytokine production in the LPS-stimulated macrophagic THP-1 cells by downregulating the activation of ERK and AP-1.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transcription Factors
/
DNA
/
RNA, Messenger
/
Enzyme-Linked Immunosorbent Assay
/
Cytokines
/
Interleukin-8
/
Interleukin-6
/
Transcription Factor AP-1
/
Interleukin-12
/
Chemokine CCL2
Limits:
Humans
Language:
English
Journal:
International Journal of Oral Biology
Year:
2017
Type:
Article
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