Blockade of TGF-β-activated kinase 1 prevents advanced glycation end products-induced inflammatory response in macrophages. (February 2016)

• Record Type: Journal Article
• Authors: Xu, Xingxin; Qi, Xiangming; Shao, Yunxia; Li, Yuanyuan; Fu, Xin; Feng, Shiyao; Wu, Yonggui
• Is Part Of: Cytokine. Volume 78(2016)
• Page Start: 62
• Page End: 68
• Publication Date: 2016-02
• Subjects: AGEs advanced glycation end products -- DN diabetic nephropathy -- TAK1 TGF-β-activated kinase 1 -- BMMs bone marrow-derived macrophages -- MAPKs mitogen-activated protein kinases -- NF-κB nuclear factor kappa B protein -- MCP-1 monocyte chemo-attractant protein-1 -- TNF-α tumor necrosis factor-alpha -- IL-1β interleukin-1 beta -- MAP3K7 mitogen-activated protein kinase kinase kinase 7 -- BMP bone morphogenetic protein -- TABs TAK1-binding proteins.; TAK1 -- MAPK -- NF-κB -- Advanced glycation end products -- Diabetic nephropathy -- Inflammation; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.11.023
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: AGE-activated macrophages in the progression of diabetic nephropathy. TAK1 plays a vital role in innate immune responses and inflammation. TAK1 inhibitor inhibit AGEs-induced macrophage activation to down-regulate inflammation via MAPKs and NF-κB pathways. 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.