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A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production

Ai Minamidate1, Michio Onizawa1,2, Chikako Saito2

  • 1Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.

Biochemistry and Biophysics Reports
|July 21, 2021
PubMed

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.

Keywords:
ADAM 17, disintegrin and metalloproteinase domain-containing protein 17CME, clathrin-mediated endocytosisEndocytosisIK, ikarugamycinIkarugamycinInflammationLPS, lipopolysaccharideTAPI-1, TNF alpha processing inhibitor-1TNFTNF, tumor necrosis factor-αTNFR, TNF receptormTNF, membrane form of TNFsTNF, soluble TNF

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