title: Blockade of TGF-β-activated kinase 1 prevents advanced glycation end products-induced inflammatory response in macrophages.
abstract: Advanced glycation end products (AGEs), inflammatory-activated macrophages are essential in the initiation and progression of diabetic nephropathy (DN). TGF-β-activated kinase 1 (TAK1) plays a vital role in innate immune responses and inflammation. However, little information has been available about the effects of AGEs on the regulation of TAK1 expression and underlying mechanisms in AGEs-stimulated macrophage activation. We hypothesized TAK1 signal pathway in AGEs conditions could be a vital factor contributing to macrophage activation and inflammation. Thus, in the present study, we used bone marrow-derived macrophages (BMMs) to explore the functional role and potential mechanisms of TAK1 pathway under AGEs conditions. Results indicated that TAK1 played important roles in AGEs-induced mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B protein (NF-κB) activation, which regulated the production of monocyte chemo-attractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) in AGEs-stimulated macrophages. The results also suggested that TAK1 inhibitor (5Z-7-oxozeaenol) could inhibit AGEs-induced macrophage activation to down-regulate inflammatory cytokine production via MAPKs and NF-κB pathways, indicating that 5Z-7-oxozeaenol might be an immunoregulatory agent against AGEs-stimulated inflammatory response in DN.
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Xingxin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: Shiyao
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, PR China. Electronic address: wuyonggui@medmail.com.cn.
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000503:physiopathology; D015536:Down-Regulation; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007249:Inflammation; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015025:Zearalenone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000008:administration & dosage; D000099151:MAP Kinase Kinase Kinase 7; D007783:Lactones; D012118:Resorcinols
chemical_list: D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D015025:Zearalenone; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols; C491768:Ccl2 protein, mouse
keywords: Advanced glycation end products; Diabetic nephropathy; Inflammation; MAPK; NF-κB; TAK1