Inhibition of Lipopolysaccharide-stimulated Inflammatory Cytokine Production by LY303511 in Human Macrophagic THP-1 Cells.
10.11620/IJOB.2017.42.3.117
- Author:
So Hee KIM
1
;
Yun Woong PAEK
;
In Chol KANG
Author Information
1. Department of Oral Microbiology, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea. ickang@jnu.ac.kr
- Publication Type:Original Article
- Keywords:
LY303511;
THP-1;
cytokine;
mitogen-activated protein kinase;
AP-1;
NF-κB
- MeSH:
Chemokine CCL2;
Cytokines;
DNA;
Enzyme-Linked Immunosorbent Assay;
Human Umbilical Vein Endothelial Cells;
Humans*;
Interleukin-12;
Interleukin-6;
Interleukin-8;
Mitogen-Activated Protein Kinases;
Phosphatidylinositol 3-Kinase;
RNA, Messenger;
Transcription Factor AP-1;
Transcription Factors
- From:International Journal of Oral Biology
2017;42(3):117-121
- CountryRepublic of Korea
- Language:English
-
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.
