کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8956312 | 1646146 | 2018 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulatory role of IKKÉ in myocardial ischemia/reperfusion injury by the determination of M1 versus M2 polarization of macrophages
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
The IκB kinase (IKK) complex plays a well-documented role in cancer and immune system. This function has been widely attributed to its role as the master regulator of the NF-κB family. Particularly, IKKÉ, a member of IKK complex, is reported to have various regulating effects in inflammatory and malignant diseases. However, its role as well as its mechanism of function in macrophages following myocardial ischemia and reperfusion (I/R) injury remains unexplored. In vivo, sham or I/R operations were performed on macrophage-specific IKKÉ knockout (mIKKÉâ/â) mice and their IKKÉflox/flox littermates. We ligated the left anterior descending (LAD) coronary artery of I/R groups simulating ischemia for 30â¯min, followed by a reperfusion period of 3â¯days and 7â¯days, respectively. The hearts of mIKKÉâ/â mice exhibited significantly increased inflammation and macrophage aggregation as compared to their IKKÉflox/flox littermates. Moreover, in the mIKKÉâ/â group subjected to I/R macrophages had a tendency to polarize to M1 phenotype. In vitro, we stimulated RAW264.7 cells with Lipopolysaccharides (LPS) after infection by the lentivirus, either knocking-down or overexpressing IKKÉ. We discovered that a deficiency of IKKÉ in RAW264.7 caused increased expression of pro-inflammatory markers compared to normal RAW264.7 after LPS stimulation. Inversely, pro-inflammatory factors were inhibited with IKKÉ overexpression. Mechanistically, IKKÉ directly combined with RelB to regulate macrophage polarization. Furthermore, IKKÉ regulated MEK1/2-ERK1/2 and downstream p65 signaling cascades after LPS stimulation. Overall, our data reveals that IKKÉ is a novel mediator protecting against the development of myocardial I/R injury via negative regulation of macrophage polarization to M1 phenotype. Thus, IKKÉ may serve as a valuable therapeutic target for the treatment of myocardial I/R injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 123, October 2018, Pages 1-12
Journal: Journal of Molecular and Cellular Cardiology - Volume 123, October 2018, Pages 1-12
نویسندگان
Yide Cao, Yueyue Xu, Merveesh Luveanand Auchoybur, Wen Chen, Shuai He, Wei Qin, Cunhua Su, Fuhua Huang, Zhibing Qiu, Liangpeng Li, Xin Chen,