Suppressive Effects of 4-(Phenylsulfanyl) Butan-2-One on CCL-1 Production via Histone Acetylation in Monocytes

Author:

Tsai Ming-Kai,Tsai Mei-Lan,Wen Zhi-HongORCID,Liao Wei-TingORCID,Lin Yi-ChingORCID,Chiou Hsin-Ying Clair,Lin Ming-HongORCID,Hung Chih-HsingORCID

Abstract

The 4-(phenylsulfanyl) butan-2-one (4-PSB-2), a marine-derived compound from soft coral, was proven to have multiple biological activities including neuroprotection and potent anti-inflammatory effects. CC chemokine ligand (CCL)-1 belongs to T helper (Th)2-related chemokines that are involved in the recruitment of Th2 inflammatory cells. Histone acetylation has been recognized as a critical mechanism underlying the regulated cytokine and chemokine production. Our study tried to investigate the anti-inflammatory effect of 4-PSB-2 on CCL-1 production in human monocytes and explore possible underlying intracellular processes, including epigenetic regulation. To confirm our hypothesis, human monocyte THP-1 cell line and primary CD14+ cells were pretreated with various concentrations of 4-PSB-2 and then were stimulated with lipopolysaccharide (LPS). The CCL-1 concentration was measured by enzyme-linked immunosorbent assays, and the intracellular signaling pathways and epigenetic regulation of 4-PSB-2 were investigated by using Western blotting and chromatin immunoprecipitation analysis. In this study, we found that 4-PSB-2 had a suppressive effect on LPS-induced CCL-1 production. Moreover, this suppressive effect of 4-PSB-2 was mediated via intracellular signaling such as the mitogen-activated protein kinase and nuclear factor-κB pathways. In addition, 4-PSB-2 could suppress CCL-1 production by epigenetic regulation through downregulating histone H3 and H4 acetylation. In short, our study demonstrated that 4-PSB-2 may have a potential role in the treatment of allergic inflammation.

Funder

Kaohsiung Armed Forces General Hospital

Ministry of Science and Technology of the Republic of China

Kaohsiung Municipal Siaogang Hospital

Publisher

MDPI AG

Subject

Microbiology (medical),Molecular Biology,General Medicine,Microbiology

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