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A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production.

Authors :: Minamidate A
Onizawa M
Saito C
Hikichi R
Mochimaru T
Murakami M
Sakuma C
Asakawa T
Hiraoka Y
Oshima S
Nagaishi T
Tsuchiya K
Ohira H
Okamoto R
Watanabe M
Source :: Biochemistry and biophysics reports [Biochem Biophys Rep] 2021 Jul 08; Vol. 27, pp. 101065. Date of Electronic Publication: 2021 Jul 08 (Print Publication: 2021).
Publication Year :: 2021
Abstract: 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.<br />Competing Interests: The authors have declared that no competing interests exist.<br /> (© 2021 The Author(s).)