The pattern recognition receptor, Mincle, is essential for maintaining the M1 macrophage phenotype in acute renal inflammation
Publication in refereed journal


引用次數
替代計量分析
.

其它資訊
摘要Mincle (macrophage-inducible C-type lectin, Clec4e) is a transmembrane pattern recognition receptor involving the innate immunity, but its role in kidney disease is still unexplored. In the obstructed kidney of the unilateral ureteral obstruction model of renal injury, Mincle was specifically detected in the infiltrating M1 macrophages (CD68(+)iNOS(+) cells) on day one but was rapidly reduced following reduction of M1 macrophages during the progression of kidney injury. Interestingly, Mincle-expressing macrophages were progressively increased in the cisplatin-induced acute kidney injury model, where iNOS expression was detected in the CD68(+) cells following Mincle induction. Adaptive transfer of Mincle(+) M1 macrophages largely promoted cisplatin-induced renal inflammation, which was prevented by the knockdown of Mincle in the transferred cells. Mincle was tightly regulated by TLR4/NF-κB signaling as evidenced by the binding of NF-κB/p65 to the promoter region of Mincle in LPS-primed macrophages. Blocking TLR4 or NF-κB suppressed LPS-induced Mincle expression on macrophages. Importantly, Mincle was found to be essential for maintaining the inflammatory phenotypes of M1 macrophages through the Syk signaling pathway since knockdown of Mincle or inhibition of Syk suppressed LPS-induced IL-1β, MCP-1, and iNOS expression. Thus, Mincle is induced specifically on M1 macrophages, where Mincle-Syk signaling promotes and maintains inflammatory phenotypes of M1 macrophages in acute renal inflammation. Hence, targeting Mincle may be a novel therapy for acute kidney injury associated with M1 macrophages.
出版社接受日期13.10.2016
著者Lv LL, Tang PM, Li CJ, You YK, Li J, Huang XR, Ni J, Feng M, Liu BC, Lan HY
期刊名稱Kidney international
出版年份2017
月份3
卷號91
期次3
頁次587 - 602
國際標準期刊號0085-2538
語言英式英語
關鍵詞Clec4e, M1 macrophage, Mincle, TLR4/NF-κB/Syk signaling, acute kidney injury, inflammation, macrophage-inducible C-type lectin

上次更新時間 2020-27-11 於 02:11