title: Advanced glycation end products and lipopolysaccharide synergistically stimulate proinflammatory cytokine/chemokine production in endothelial cells via activation of both mitogen-activated protein kinases and nuclear factor-kappaB.
abstract: It has been well documented that both endogenous inflammatory mediator advanced glycation end products (AGEs) and exogenous inflammatory inducer lipopolysaccharide play key roles in the initiation and development of inflammatory diseases. However, the combined inflammation-stimulatory effect of AGEs and lipopolysaccharide on endothelial cells, and, furthermore, the underlying signal transduction pathways involved, have not been fully elucidated. We found that in vitro co-stimulation with AGE-human serum albumin (HSA) and lipopolysaccharide exhibits a synergistic effect on proinflammatory cytokine/chemokine interleukin-6, interleukin-8 and monochemoattractant protein-1 production in human umbilical vein endothelial cells. Similar to lipopolysaccharide, AGE-HSA stimulation induced mitogen-activated protein kinase phosphorylation and nuclear factor-kappaB nuclear translocation in human umbilical vein endothelial cells, which was further enhanced by a combination of the two stimulants. Pharmacological inhibitions of each individual signaling pathway, including p38, extracellular signal-regulated kinase 1/2, Jun N-terminal kinase and nuclear factor-kappaB, revealed that activation of all of these four pathways is necessary for the effective induction of interleukin-6, interleukin-8 and monochemoattractant protein-1 by both AGE-HSA and lipopolysaccharide. These results suggest that AGEs and lipopolysaccharide cooperatively induce proinflammatory cytokine/chemokine production by activating mitogen-activated protein kinases and nuclear factor-kappaB in endothelial cells, thus amplifying the inflammatory response and resulting in tissue damage.
authors: Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, China.
authors: Jinghua
authors: J
authors: Liu
authors: Shanchao
authors: S
authors: Zhao
authors: Jing
authors: J
authors: Tang
authors: Zhijie
authors: Z
authors: Li
authors: Tianyu
authors: T
authors: Zhong
authors: Yawei
authors: Y
authors: Liu
authors: Dengyu
authors: D
authors: Chen
authors: Mingzhe
authors: M
authors: Zhao
authors: Yusheng
authors: Y
authors: Li
authors: Xiaowei
authors: X
authors: Gong
authors: Peng
authors: P
authors: Deng
authors: Jiang H
authors: JH
authors: Wang
authors: Yong
authors: Y
authors: Jiang
mesh_terms: D021581:Active Transport, Cell Nucleus; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D004357:Drug Synergism; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D015398:Signal Transduction
chemical_list: D018925:Chemokines; D016207:Cytokines; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012709:Serum Albumin; C109748:advanced glycation end products-human serum albumin; D020928:Mitogen-Activated Protein Kinases; D000075462:Serum Albumin, Human