Regulatory role of IKKɑ in myocardial ischemia/reperfusion injury by the determination of M1 versus M2 polarization of macrophages

Journal of Molecular and Cellular Cardiology
Yide CaoXin Chen

Abstract

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, IKKɑ, 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 IKKɑ knockout (mIKKɑ-/-) mice and their IKKɑflox/flox littermates. We ligated the left anterior descending (LAD) coronary artery of I/R groups simulating ischemia for 30 min, followed by a reperfusion period of 3 days and 7 days, respectively. The hearts of mIKKɑ-/- mice exhibited significantly increased inflammation and macrophage aggregation as compared to their IKKɑflox/flox littermates. Moreover, in the mIKKɑ-/- 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 IKKɑ. We discovered that a deficiency of IKKɑ in RAW264.7 caused inc...Continue Reading

Citations

Jun 10, 2020·Journal of Receptor and Signal Transduction Research·Xin-Zhou DengZhi-Guo Luo
Sep 25, 2019·International Journal of Molecular Sciences·Béla KovácsElőd Ernő Nagy
Jul 6, 2019·Cardiology Research and Practice·Nan-Bo LiuXiao-Kang Li

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