The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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FSL-1, a Toll-like Receptor 2/6 Agonist, Induces Expression of Interleukin-$1{\alpha}$ in the Presence of 27-hydroxycholesterol

  • Heo, Weon (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Sun-Mi (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Eo, Seong-Kug (College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Rhim, Byung-Yong (Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Koanhoi (Department of Pharmacology, Pusan National University School of Medicine)
  • Received : 2014.06.13
  • Accepted : 2014.08.25
  • Published : 2014.12.30
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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 $IL-1{\alpha}$ 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 $IL-1{\alpha}$. Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and $IL-1{\alpha}$. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and $IL-1{\alpha}$ induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of $IL-1{\alpha}$. These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of $IL-1{\alpha}$ in monocytic cells via multiple signaling pathways.

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References

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