Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway

International Journal of Molecular Sciences

Yi-Chen Wang³  Han-Chun Hung²  Chien-Wei Feng²  Shi-Ying Huang⁵  Chun-Hong Chen²  Yen-You Lin³  Yao-Chang Chen⁴  San-Nan Yang⁶  Jui-Hsin Su¹  Jyh-Horng Sheu³  Zhi-Hong Wen² 

[1] National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan; E-Mail:;Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan; E-Mails:;Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; E-Mails:;Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan; E-Mail:;Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; E-Mail:;School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 84001, Taiwan; E-Mail:

关键词: marine compounds;    macrophage;    foam cell;    lysosome;    cyclic adenosine monophosphate (cAMP);    transforming growth factor β1 (TGF-β1);   

DOI  :  10.3390/ijms160510507

来源: mdpi

【 摘 要 】

Atherosclerosis 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.