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KMID : 0811720140180060475
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Korean Journal of Physiology & Pharmacology
2014 Volume.18 No. 6 p.475 ~ p.480
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FSL-1, a Toll-like Receptor 2/6 Agonist, Induces Expression of Interleukin-1α in the Presence of 27-hydroxycholesterol
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Heo Weon
Kim Sun-Mi
Eo Seong-Kug
Rhim Byung-Yong
Kim Koan-Hoi
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Abstract
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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-1α 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-1α. Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and IL-1α. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and IL-1α induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of IL-1α. These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of IL-1α in monocytic cells via multiple signaling pathways.
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KEYWORD
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27-Hydroxycholesterol, Interleukin-1, Monocytes/macrophages, TLR-6
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