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Article

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

by
Yi-Chen Wang
1,2,†,
Han-Chun Hung
3,†,
Chien-Wei Feng
3,
Shi-Ying Huang
4,
Chun-Hong Chen
3,
Yen-You Lin
1,
Yao-Chang Chen
5,
San-Nan Yang
6,
Jui-Hsin Su
7,
Jyh-Horng Sheu
1,8,9,* and
Zhi-Hong Wen
3,10,*
1
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
2
Division of Cardiology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan
3
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan
4
Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
5
Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan
6
School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 84001, Taiwan
7
National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan
8
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
9
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
10
Marine Biomedical Laboratory & Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2015, 16(5), 10507-10525; https://doi.org/10.3390/ijms160510507
Submission received: 17 March 2015 / Revised: 22 April 2015 / Accepted: 29 April 2015 / Published: 7 May 2015
(This article belongs to the Special Issue Bioactivity of Marine Natural Products)
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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.
Keywords: marine compounds; macrophage; foam cell; lysosome; cyclic adenosine monophosphate (cAMP); transforming growth factor β1 (TGF-β1) marine compounds; macrophage; foam cell; lysosome; cyclic adenosine monophosphate (cAMP); transforming growth factor β1 (TGF-β1)

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MDPI and ACS Style

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.; et al. 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. https://doi.org/10.3390/ijms160510507

AMA Style

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, et al. 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. https://doi.org/10.3390/ijms160510507

Chicago/Turabian Style

Wang, Yi-Chen, 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, and et al. 2015. "Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway" International Journal of Molecular Sciences 16, no. 5: 10507-10525. https://doi.org/10.3390/ijms160510507

APA Style

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. (2015). Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway. International Journal of Molecular Sciences, 16(5), 10507-10525. https://doi.org/10.3390/ijms160510507

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