Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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7α-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells

  • Seo, Hyun Chul (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 : 2014.06.05
  • Accepted : 2014.09.01
  • Published : 2015.01.01
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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. $7{\alpha}$-Hydroxycholesterol ($7{\alpha}OHChol$) 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 $7{\alpha}OHChol$ 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 $7{\beta}$-hydroxycholesterol ($7{\beta}OHChol$) did not affect TLR6 expression, and addition of FSL-1 to cells treated with either 7K or $7{\beta}OHChol$ did not influence transcription of the genes. Pharmacological inhibition of ERK, Akt, or PI3K resulted in attenuated transcription of TLR6 induced by $7{\alpha}OHChol$ as well as secretion of IL-23 enhanced by $7{\alpha}OHChol$ 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 $7{\alpha}OHChol$ can elicit TLR6-mediated expression of IL-23 by monocytic cells via PI3K/Akt and MAPKs pathways.

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References

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