A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production

Ai Minamidate; Michio Onizawa; Chikako Saito; Rie Hikichi; Tomoaki Mochimaru; Mai Murakami; Chiharu Sakuma; Takehito Asakawa; Yuichi Hiraoka; Shigeru Oshima; Takashi Nagaishi; Kiichiro Tsuchiya; Hiromasa Ohira; Ryuichi Okamoto; Mamoru Watanabe

Biochemistry and Biophysics Reports (Sep 2021)

A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production

Ai Minamidate,
Michio Onizawa,
Chikako Saito,
Rie Hikichi,
Tomoaki Mochimaru,
Mai Murakami,
Chiharu Sakuma,
Takehito Asakawa,
Yuichi Hiraoka,
Shigeru Oshima,
Takashi Nagaishi,
Kiichiro Tsuchiya,
Hiromasa Ohira,
Ryuichi Okamoto,
Mamoru Watanabe

Affiliations

Ai Minamidate: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Michio Onizawa: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan; Corresponding author. Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Chikako Saito: Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan
Rie Hikichi: Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan
Tomoaki Mochimaru: Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan
Mai Murakami: Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan
Chiharu Sakuma: Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan
Takehito Asakawa: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Yuichi Hiraoka: Laboratory of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Laboratory of Genome Editing for Biomedical Research, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
Shigeru Oshima: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Takashi Nagaishi: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Kiichiro Tsuchiya: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
Hiromasa Ohira: Department of Gastroenterology and Hepatology, Fukushima Medical University, Fukushima, Japan
Ryuichi Okamoto: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
Mamoru Watanabe: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Corresponding author. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.

Journal volume & issue: Vol. 27
p. 101065

Abstract

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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.

Published in Biochemistry and Biophysics Reports

ISSN: 2405-5808 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: http://www.journals.elsevier.com/biochemistry-and-biophysics-reports/

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