Minamidate Ai, Onizawa Michio, Saito Chikako, Hikichi Rie, Mochimaru Tomoaki, Murakami Mai, Sakuma Chiharu, Asakawa Takehito, Hiraoka Yuichi, Oshima Shigeru, Nagaishi Takashi, Tsuchiya Kiichiro, Ohira Hiromasa, Okamoto Ryuichi, Watanabe Mamoru
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan.
Biochem Biophys Rep. 2021 Jul 8;27:101065. doi: 10.1016/j.bbrep.2021.101065. eCollection 2021 Sep.
Ikarugamycin (IK) is an antibiotic which has been reported to have a variety of functions, such as inhibition of clathrin-mediated endocytosis (CME), anti-tumor effects and regulation of the immune system. Whether IK influences cytokine production is poorly understood. We have investigated the relationship between IK and production of tumor necrosis factor-α (TNF). TNF plays a pivotal role in pathogenesis of many diseases. Although the dynamics of soluble TNF (sTNF) has been widely explored so far, the functions of the membrane form of TNF (mTNF) have not been fully elucidated. We demonstrated that IK increases the amount of mTNF and prolongs the duration of TNF expression. This effect is unrelated to the shedding activity of disintegrin and metalloproteinase domain-containing protein 17 (ADAM 17). Our results revealed that there is a mechanism to terminate inflammation at the cellular level which IK dysregulates. Furthermore, IK can be a tool to study TNF signaling due to its effect of increasing mTNF expression.
刺参霉素（IK）是一种抗生素，据报道它具有多种功能，如抑制网格蛋白介导的内吞作用（CME）、抗肿瘤作用和调节免疫系统。IK是否影响细胞因子的产生尚不清楚。我们研究了IK与肿瘤坏死因子-α（TNF）产生之间的关系。TNF在许多疾病的发病机制中起关键作用。尽管迄今为止对可溶性TNF（sTNF）的动态变化已进行了广泛研究，但TNF膜形式（mTNF）的功能尚未完全阐明。我们证明IK增加了mTNF的量并延长了TNF表达的持续时间。这种作用与含解整合素和金属蛋白酶结构域蛋白17（ADAM 17）的脱落活性无关。我们的结果表明，在细胞水平上存在一种终止炎症的机制，而IK使其失调。此外，由于IK具有增加mTNF表达的作用，它可以成为研究TNF信号传导的一种工具。
