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.
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Authors | Xingxin Xu, Xiangming Qi, Yunxia Shao, Yuanyuan Li, Xin Fu, Shiyao Feng, Yonggui Wu |
Journal | Cytokine
(Cytokine)
Vol. 78
Pg. 62-8
(Feb 2016)
ISSN: 1096-0023 [Electronic] England |
PMID | 26687627
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- 7-oxozeanol
- Ccl2 protein, mouse
- Chemokine CCL2
- Glycation End Products, Advanced
- NF-kappa B
- Tumor Necrosis Factor-alpha
- Zearalenone
- MAP Kinase Kinase Kinases
- MAP kinase kinase kinase 7
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Topics |
- Animals
- Cells, Cultured
- Chemokine CCL2
(metabolism)
- Diabetic Nephropathies
(physiopathology)
- Down-Regulation
- Glycation End Products, Advanced
(metabolism)
- Inflammation
- MAP Kinase Kinase Kinases
(antagonists & inhibitors, deficiency)
- Macrophage Activation
- Macrophages
(immunology)
- Mice
- NF-kappa B
(metabolism)
- Signal Transduction
- Tumor Necrosis Factor-alpha
(metabolism)
- Zearalenone
(analogs & derivatives, pharmacology)
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