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: 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)
• 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

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)