A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression
Jialin Dai, Chonghe Zhang, Lin Guo, Hao He, Kai Jiang, Yingying Huang, Xixi Zhang, Haibing Zhang, Wei Wu, Yaoyang Zhang, Lihua Lu, Junhao Hu
Abstract
Mixed-lineage kinase domain-like protein (MLKL) is known as the terminal executor of necroptosis. However, its function outside of necroptosis is still not clear. Herein, we demonstrate that MLKL promotes vascular inflammation by regulating the expression of adhesion molecules ICAM1, VCAM1, and E-selectin in endothelial cells (EC). MLKL deficiency suppresses the expression of these adhesion molecules, thereby reducing EC-leukocyte interaction in vitro and in vivo. Mechanistically, we show that MLKL interacts with RBM6 to promote the mRNA stability of adhesion molecules. In conclusion, this study identified a novel role of MLKL in regulating endothelial adhesion molecule expression and local EC-leukocyte interaction during acute inflammation.