|
KMID : 0606920110190030302
|
|
Biomolecules & Therapeutics
2011 Volume.19 No. 3 p.302 ~ p.307
|
|
|
Cellular Signaling Molecules Associated with Peptidoglycan- Induced CCL3 Up-Regulation
|
|
Kim Kang-Seung
Rhim Byung-Yong
Eo Seong-Kug
Kim Koan-Hoi
|
|
|
Abstract
|
|
|
|
Peptidoglycan (PGN) is detected in infl ammatory 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 infl ammatory 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 signifi cantly attenuated PGN-mediated CCL3 up-regulation. However, polymyxin B, LY294002, and SB202190 did not infl uence 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.
|
|
|
KEYWORD
|
|
|
CCL3, Macrophages, Peptidoglycan
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|