Kim Ji-Youn, Jee Hyeon-Gun, Kim Ju Yeong, Yong Tai-Soon, Jeon Soung-Hoo
Division of Oral & Maxillofacial Surgery, Department of Dentistry, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea.
Department of Tropical Medicine, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Biochem Biophys Rep. 2024 Feb 6;38:101659. doi: 10.1016/j.bbrep.2024.101659. eCollection 2024 Jul.
Proinflammatory cytokine plays a central role in host defense and acute inflammatory responses. Both positive and negative correlations of NF-κB and Wnt/β-catenin pathways have been reported depending on cell types in response to inflammatory stimuli for IL-6 cytokine production. Macrophages are vital to the regulation of immune responses and the development of inflammation, but the crosstalk between two pathways has not been elucidated so far in macrophages. We observed a positive cross-regulation between the NF-κB and Wnt/β-catenin pathways for IL-6 production in human macrophages. To verify the functional validity of this interaction, LY294002 or PNU74654, representative blockers of each pathway, were treated. IL-6 secretion was reduced to the basal level by both inhibitor treatments, even when stimulated by LPS. We also found that NF-κB p65 migrated to the nucleus and interacted with the transcription factor TCF-4 in macrophages upon LPS stimulation.
促炎细胞因子在宿主防御和急性炎症反应中起核心作用。根据细胞类型对炎症刺激产生白细胞介素-6细胞因子的反应，已报道核因子κB（NF-κB）和Wnt/β-连环蛋白信号通路存在正相关和负相关。巨噬细胞对免疫反应的调节和炎症的发展至关重要，但到目前为止，巨噬细胞中这两条信号通路之间的相互作用尚未阐明。我们观察到在人类巨噬细胞中，NF-κB和Wnt/β-连环蛋白信号通路之间对白细胞介素-6的产生存在正向交叉调节。为了验证这种相互作用的功能有效性，使用了每条信号通路的代表性阻滞剂LY294002或PNU74654进行处理。即使在受到脂多糖（LPS）刺激时，两种抑制剂处理均使白细胞介素-6分泌降至基础水平。我们还发现，在LPS刺激下，巨噬细胞中的NF-κB p65迁移至细胞核并与转录因子TCF-4相互作用。
