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

Abstract

Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-a and interleukin-1a (IL-1a), trigger the activation of the transcription factor nuclear factor-jB, 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-a more strongly than that induced by IL-1a 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-a-induced ICAM-1 expression at lower concentrations than the IL-1a-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.

Ursolic acid, a natural pentacyclic triterpenoid, inhibits intracellular trafficking of proteins and induces accumulation of intercellular adhesion molecule‐1 linked to high‐mannose‐type glycans in the endoplasmic reticulum

“…Human lung carcinoma A549 cells and human breast adenocarcinoma MCF‐7 cells were induced to express ICAM‐1 in response to IL‐1α stimulation [31,32]. A549 cells and MCF‐7 cells were preincubated with ursolic acid for 1 h and then incubated with IL‐1α for 6 h. Then, the amount of cell‐surface ICAM‐1 was quantitated by the Cell‐ELISA assay.…”

Role of the junctional epithelium in periodontal innate defense and homeostasis

“…Our previous study indicated the expression of ICAM‐1 in the junctional epithelium but not in the oral gingival epithelium of germ‐free mice (12). The expression of ICAM‐1 in epithelial cells is regulated by proinflammatory cytokines such as IL‐1 and TNF‐α (28,29). Our study indicated the constitutive expression of these molecules in the junctional epithelium of germ‐free mice, whereas the oral sulcular epithelium showed almost no expression of these molecules.…”

Cardenolide Aglycones Inhibit Tumor Necrosis Factor α-Induced Expression of Intercellular Adhesion Molecule-1 at the Translation Step by Blocking Na+/K+-ATPase

“…33,34) We have recently shown that ouabain strongly inhibits the TNF-α-induced cell-surface expression of ICAM-1 in A549 cells. 26) Ouabagenin was found to inhibit the TNF-α-induced ICAM-1 expression in a dose-dependent manner; its IC 50 value was 7.5 µM (Fig.…”

“…33,34) Cell-surface ICAM-1 (%) was calculated using the following formula: {(test sample−background)/(sample with TNF-α−background)}×100.…”

“…The MTT assay was performed as described previously. 33,34) Crystal violet (%) and MTT reduction (%) were calculated using the following formula: {(test sample−background)/(control without TNF-α− background)}×100.…”