title: Peptidoglycan Up-Regulates CXCL8 Expression via Multiple Pathways in Monocytes/Macrophages.
abstract: Peptidoglycan (PG), the gram positive bacterial pathogen-associated molecular patterns (PAMP), is detected in a high proportion in macrophage-rich atheromatous regions, and expression of chemokine CXCL8, which triggers monocyte arrest on early atherosclerotic endothelium, is elevated in monocytes/macrophages in human atherosclerotic lesion. The aim of this study was to investigate whether PG induced CXCL8 expression in the cell type and to determine cellular signaling pathways involved in that process. Exposure of THP-1 cell, human monocyte/macrophage cell line, to PG not only enhanced CXCL8 release but also profoundly induced il8 gene transcription. PG-induced release of CXCL8 and induction of il8 gene transcription were blocked by OxPAPC, an inhibitor of TLR-2/4 and TLR4, but not by polymyxin B, an inhibitor of LPS. PG-mediated CXCL8 release was significantly attenuated by inhibitors of PI3K-Akt-mTOR pathways. PKC inhibitors, MAPK inhibitors, and ROS quenchers also significantly attenuated expression of CXCL8. The present study proposes that PG contributes to inflammatory reaction and progression of atherosclerosis by inducing CXCL8 expression in monocytes/macrophages, and that TLR-2, PI3K-Akt-mTOR, PKC, ROS, and MAPK are actively involved in the process.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Republic of Korea ; Medical Research Institute, Pusan National University Hospital, Pusan 602-739, Republic of Korea.
authors.forename: Chung Won
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Republic of Korea.
authors.forename: Sung Woon
authors.initials: SW
authors.lastname: Chung
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Republic of Korea.
authors.forename: Mi Ju
authors.initials: MJ
authors.lastname: Bae
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Republic of Korea.
authors.forename: Seunghwan
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Republic of Korea.
authors.forename: Sang-Pil
authors.initials: SP
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Pusan National University - School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
keywords: CXCL8; Monocytes/Macrophages; PI3K; Peptidoglycan