We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway.
- Authors
Yi-Chen Wang; Han-Chun Hung; Chien-Wei Feng; Shi-Ying Huang; Chun-Hong Chen; Yen-You Lin; Yao-Chang Chen; San-Nan Yang; Jui-Hsin Su; Jyh-Horng Sheu; Zhi-Hong Wen
- Abstract
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.
- Subjects
ATHEROSCLEROSIS treatment; SULFONE derivatives; MACROPHAGES; CYCLOOXYGENASE 2; TRANSFORMING growth factors-beta; ADENOSINE monophosphate; PHYSIOLOGY
- Publication
International Journal of Molecular Sciences, 2015, Vol 16, Issue 5, p10507
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms160510507