Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway
AbstractAtherosclerosis is considered an inflammatory disease. However, clinically used anti-atherosclerotic drugs, such as simvastatin, have many side effects. Recently, several unique marine compounds have been isolated that possess a variety of bioactivities. In a previous study, we found a synthetic precursor of the marine compound (austrasulfone), which is dihydroaustrasulfone alcohol (WA-25), has anti-atherosclerotic effects in vivo. However, the detailed mechanisms remain unclear. Therefore, to clarify the mechanisms through which WA-25 exerts anti-atherosclerotic activity, we used RAW 264.7 macrophages as an in vitro model to evaluate the effects of WA-25. In lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, WA-25 significantly inhibited expression of the pro-inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In contrast, simvastatin increased the COX-2 expression compared to WA-25. In addition, WA-25 impedes foam cell formation and up-regulated the lysosomal and cyclic adenosine monophosphate (cAMP) signaling pathway. We also observed that transforming growth factor β1 (TGF-β1) was up-regulated by WA-25 and simvastatin in LPS-induced RAW 264.7 cells, and the promising anti-atherosclerosis effects of WA-25 were disrupted by blockade of TGF-β1 signaling. Besides, WA-25 might act through increasing lipolysis than through alteration of lipid export. Taken together, these data demonstrate that WA-25 may have potential as an anti-atherosclerotic drug with anti-inflammatory effects. View Full-Text
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Wang, Y.-C.; Hung, H.-C.; Feng, C.-W.; Huang, S.-Y.; Chen, C.-H.; Lin, Y.-Y.; Chen, Y.-C.; Yang, S.-N.; Su, J.-H.; Sheu, J.-H.; Wen, Z.-H. Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway. Int. J. Mol. Sci. 2015, 16, 10507-10525.
Wang Y-C, Hung H-C, Feng C-W, Huang S-Y, Chen C-H, Lin Y-Y, Chen Y-C, Yang S-N, Su J-H, Sheu J-H, Wen Z-H. Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway. International Journal of Molecular Sciences. 2015; 16(5):10507-10525.Chicago/Turabian Style
Wang, Yi-Chen; Hung, Han-Chun; Feng, Chien-Wei; Huang, Shi-Ying; Chen, Chun-Hong; Lin, Yen-You; Chen, Yao-Chang; Yang, San-Nan; Su, Jui-Hsin; Sheu, Jyh-Horng; Wen, Zhi-Hong. 2015. "Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway." Int. J. Mol. Sci. 16, no. 5: 10507-10525.