7alpha-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells.
10.4062/biomolther.2014.067
- Author:
Hyun Chul SEO
1
;
Sun Mi KIM
;
Seong Kug EO
;
Byung Yong RHIM
;
Koanhoi KIM
Author Information
1. Department of Pharmacology, Pusan National University - School of Medicine, Yangsan 626-870, Republic of Korea. koanhoi@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
7alpha-hydroxycholesterol;
IL-23;
Macrophages;
Toll-like receptor 6
- MeSH:
Atherosclerosis;
Cholesterol;
Interleukin-12;
Interleukin-23*;
Macrophages;
p38 Mitogen-Activated Protein Kinases;
Toll-Like Receptor 6
- From:Biomolecules & Therapeutics
2015;23(1):84-89
- CountryRepublic of Korea
- Language:English
-
Abstract:
We investigated the question of whether 7-oxygenated cholesterol derivatives could affect inflammatory and/or immune responses in atherosclerosis by examining their effects on expression of IL-23 in monocytic cells. 7alpha-Hydroxycholesterol (7alphaOHChol) induced transcription of the TLR6 gene and elevated the level of cell surface TLR6 protein in THP-1 monocytic cells. Addition of an agonist of TLR6, FSL-1, to TLR6-expressing cells by treatment with 7alphaOHChol resulted in enhanced production of IL-23 and transcription of genes encoding the IL-23 subunit alpha (p19) and the IL-12 subunit beta (p40). However, treatment with 7-ketocholesterol (7K) and 7beta-hydroxycholesterol (7betaOHChol) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or 7betaOHChol did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by 7alphaOHChol as well as secretion of IL-23 enhanced by 7alphaOHChol plus FSL-1. Inhibition of p38 MAPK or JNK resulted in attenuated secretion of IL-23. These results indicate that a certain type of 7-oxygenated cholesterol like 7alphaOHChol can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways.
