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Mycotrienin II, a translation inhibitor that prevents ICAM-1 expression induced by pro-inflammatory cytokines

Journal of Antibiotics, ISSN: 0021-8820, Vol: 64, Issue: 5, Page: 361-366
2011
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Article Description

Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin-1α (IL-1α), trigger the activation of the transcription factor nuclear factor-B, a molecule that induces the expression of a variety of genes, including intercellular adhesion molecule-1 (ICAM-1). Here, we report that mycotrienin II, a member of the triene-ansamycin group, inhibited the cell-surface ICAM-1 expression induced by TNF-α more strongly than that induced by IL-1α in human lung carcinoma A549 cells. Mycotrienin II was found to inhibit protein synthesis in intact living cells, as well as in cell-free translation systems. Among translation inhibitors tested, acetoxycycloheximide and anisomycin, but neither puromycin nor emetine, inhibited the TNF-α-induced ICAM-1 expression at lower concentrations than the IL-1α-induced ICAM-1 expression. Several compounds of the triene-ansamycin group (that is, mycotrienin I, trienomycin A, trierixin, quinotrierixin and quinotrierixin HQ) also inhibited ICAM-1 expression, as well as cell-free translation in a manner similar to mycotrienin II. These results indicate that mycotrienin II is a direct inhibitor of translation, thereby inhibiting ICAM-1 expression induced by pro-inflammatory cytokines. © 2011 Japan Antibiotics Research Association. All rights reserved.

Bibliographic Details

Yamada, Yuriko; Tashiro, Etsu; Taketani, Shigeru; Imoto, Masaya; Kataoka, Takao

Springer Science and Business Media LLC

Pharmacology, Toxicology and Pharmaceutics

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