Advanced glycation end products-induced inflammatory reaction in human monocytes:cellular receptor pathway & intracellular signaling
- VernacularTitle:晚期糖基化终产物诱导单核细胞产生细胞因子的细胞内信号传导机制
- Author:
Yang LIU
;
Shangxi LIU
;
Fanfan HOU
- Publication Type:Journal Article
- Keywords:
advanced glycosylation end products;
reactive oxygen species (ROS);
NADPH oxidase;
NF-kappa B;
interleukin-1;
tumor necrosis factor
- From:
Medical Journal of Chinese People's Liberation Army
2001;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the cellular receptor pathway and the intracellular signaling of advanced glycation end products(AGE)-induced inflammatory reaction in monocytes. Methods Human peripheral monocytes were isolated from healthy volunteers. Cells were incubated with AGE modified by the addition of human serum albumin (AGE-HSA) either with pretreatment or no pretreatment of anti-AGE receptor (RAGE) IgG, NADPH oxidase inhibitor (apocynin)or a specific inhibitor of p38(SB 203580). The levels of interleukin-1?(IL-1?)and tumor necrosis factor-?(TNF-?) in the supernatants were assayed with enzyme-linked immunoadsorbent assay (ELISA). Reactive oxygen species (ROS) production was determined by MCLA chemiluminescence. Nuclear factor-?B translocation was assayed by immunochemical staining with anti-NF-?B/p65 and electrophoretic mobility shift assay(EMSA). Results AGE-HSA was found to induce activation of NF-?B, increase levels of IL-1? and TNF-? in the supernatants, and enhance production of ROS by monocytes. Pre-treatment of cells with anti-RAGE IgG or apocynin inhibited AGE-HSA to induce NF-?B translocation and IL-1? or TNF-? production. AGE stimulated ROS production could also be blocked by pre-treatment of cultured cells with anti-RAGE IgG or apocynin. Pre-treatment of cultured cells with SB 203580 inhibited both NF-?B activation and cytokines production, but showed no significant effect the cells to produce ROS. Conclusion AGE-HSA could induce IL-1? and TNF-? release as well as ROS production in human monocytes via a pathway mediated by RAGE. Activation of NADPH oxidase may be the upstream of the intracellular pathway. AGE-induced cytokines production was p38 pathway-dependent.
