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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 117 - 121 (5page)
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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.
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참고문헌 (15)
참고문헌 신청
A. S. Kristof / 2005 / LY303511 (2-Piperazinyl-8-phenyl-4H-1-benzopyran-4-one) Acts via Phosphatidylinositol 3-Kinase-Independent Pathways to Inhibit Cell Proliferation via M
Adcock IM / 1997 / Transcription factors as activators of gene transcription : AP-1 and NF-κB / Monaldi Arch Chest Dis 52 : 178 ~ 186
Arcaro A / 1993 / Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor : the role of phosphatidylinositol 3, 4, 5-trisphosphate in neutrophil responses / Biochem J
Auwerx J / 1991 / The human leukemia cell line, THP-1 : a multifacetted model for the study of monocyte-macrophage differentiation / Experientia 47 : 22 ~ 31
Avni D / 2011 / The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 modulates cytokine expression in macrophages via p50 nuclear factor-κB inhibition, in a PI3K-inde
Adcock IM / 1997 / Transcription factors as activators of gene transcription : AP-1 and NF-κB / Monaldi Arch Chest Dis 52 : 178 ~ 186
Arcaro A / 1993 / Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor : the role of phosphatidylinositol 3, 4, 5-trisphosphate in neutrophil responses / Biochem J
Auwerx J / 1991 / The human leukemia cell line, THP-1 : a multifacetted model for the study of monocyte-macrophage differentiation / Experientia 47 : 22 ~ 31
Avni D / 2011 / The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 modulates cytokine expression in macrophages via p50 nuclear factor-κB inhibition, in a PI3K-inde
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