FSL-1, a Toll-like Receptor 2/6 Agonist, Induces Expression of Interleukin-1alpha in the Presence of 27-hydroxycholesterol
The Korean Journal of Physiology and Pharmacology
;
: 475-480, 2014.
Article
in English
| WPRIM
| ID: wpr-727697
ABSTRACT
We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the IL-1alpha gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of IL-1alpha . Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and IL-1alpha. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and IL-1alpha induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of IL-1alpha . These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of IL-1alpha in monocytic cells via multiple signaling pathways.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Cholesterol
/
Cytokines
/
Interleukin-1
/
Toll-Like Receptors
/
Interleukin-1alpha
/
Inflammation
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2014
Type:
Article
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