The endothelial damage of Kawasaki disease (KD) is linked with macrophage-mediated inflammation. KCa3.1, a calcium-activated potassium channel, regulates the inflammation of macrophages. Still, there is limited information surrounding the potential role of KCa3.1 in regulating inflammatory response by macrophages and subsequent vascular injury in an in vitro model of KD.
The study performed by F Zheng et al. showed that Lactobacillus casei cell wall extract (LCWE) increased KCa3.1 protein level in RAW264.7 macrophages and that the KCa3.1 inhibition by TRAM-34 notably suppressed the expression of pro-inflammatory molecules in LCWE-treated macrophages via blocking the activation of NF-κB and STAT3 pathways. The researchers found the inflammation and damage of mouse coronary artery endothelial cells were attenuated in the TRAM-34-treated group compared with the KD model group. This vascular protective role depended on the down-regulation of NF-κB and STAT3 signal pathways, which was confirmed by using inhibitors of NF-κB and STAT3.
The study demonstrates that the KCa3.1 blockade of macrophages suppresses inflammatory reaction leading to mouse coronary artery endothelial cell injury in a cell model of KD by hampering the activation of NF-κB and STAT3 signaling pathway. These findings imply that KCa3.1 may be a potential therapeutic target for KD.
Researchers stimulated RAW264.7 cells with LCWE with or without TRAM-34 or PDTC or AG490. Subsequently, MCAECs were incubated with RAW264.7 cells-conditioned medium to mimic local inflammatory lesions in KD. CCKi8 assay evaluated cell viability and mRNA levels of inflammatory mediators were detected by qRT-PCR. In addition, expressions of KCa3.1, MCAECs injury-associated molecules, proteins involved in signal pathways of nuclear factor-κB (NF-κB), signal transducers, and activators of transcription (STAT) 3 and p38 were evaluated by Western blot. Histone 3 was measured via Western blot using HUABIO antibody, Histone H3 Mouse Monoclonal Antibody clone 3-C4.
Zheng, Fenglei, et al. "KCa3. 1 Inhibition of Macrophages Suppresses Inflammatory Response Leading to Endothelial Damage in a Cell Model of Kawasaki Disease." Journal of Inflammation Research 14 (2021): 719.