Abstract
Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin-1α (IL-1α), trigger the activation of the transcription factor nuclear factor-κB, 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.
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Acknowledgements
We are very grateful to Drs. Kazuo Nagai, Yoshinori Tsukumo and Rei Koyanagi for their initial contributions to start this work. This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI) from Japan Society for the Promotion of Science (JSPS) and a Grant-in-Aid from the Naito Foundation.
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Yamada, Y., Tashiro, E., Taketani, S. et al. Mycotrienin II, a translation inhibitor that prevents ICAM-1 expression induced by pro-inflammatory cytokines. J Antibiot 64, 361–366 (2011). https://doi.org/10.1038/ja.2011.23
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DOI: https://doi.org/10.1038/ja.2011.23
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