Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Cellular Signaling Molecules Associated with Peptidoglycan-Induced CCL3 Up-Regulation

  • Kim, Kang-Seung (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Rhim, Byung-Yong (Department of Pharmacology, School of Medicine, Pusan National University) ;
  • Eo, Seong-Kug (Laboratory of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Kim, Koan-Hoi (Department of Pharmacology, School of Medicine, Pusan National University)
  • Received : 2011.05.17
  • Accepted : 2011.06.30
  • Published : 2011.07.31
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Abstract

Peptidoglycan (PGN) is detected in inflammatory cell-rich regions of human atheromatous plaques. The present study investigated the effects of PGN on CC chemokine ligand 3 (CCL3) expression, which is elevated in the atherosclerotic arteries, and determined cellular factors involved in PGN-mediated CCL3 up-regulation in mononuclear cells, with the goal of understanding the molecular mechanisms of inflammatory responses to bacterial pathogen-associated molecular patterns in diseased arteries. Exposure of human monocytic leukemia THP-1 cells to PGN resulted in enhanced secretion of CCL3 and profound induction of the CCL3 gene transcript. Both events were abrogated by oxidized 1-palmitoyl-2-arachidonosyl-sn-phosphatidylcholine, an inhibitor of Toll-like receptors 2/4. Pharmacological inhibitors such as U0126, SP6001250, Akt inhibitor IV, rapamycin, RO318220, diphenyleneiodonium chloride, and N-acetylcysteine also significantly attenuated PGN-mediated CCL3 up-regulation. However, polymyxin B, LY294002, and SB202190 did not influence CCL3 expression. We propose that PGN contributes to enhanced CCL3 expression in atherosclerotic plaques and that Toll-like receptors (TLR2), Akt, mTOR, mitogen-activated protein kinase, and reactive oxygen species are involved in that process.

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References

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