A novel PPARα agonist propane-2-sulfonic acid octadec-9-enyl-amide inhibits inflammation in THP-1cells

作者：Zhao, Yun; Yan, Lu; Luo, Xiu-Mei; Peng, Lu; Guo, Han; Jing, Zuo; Yang, Li-Chao; Hu, Rong; Wang, Xuan; Huang, Xue-Feng; Wang, Yi-Qing^*; Jin, Xin^*

来源：European Journal of Pharmacology, 2016, 788: 104-112.

DOI：10.1016/j.ejphar.2016.06.026

• Propane-2-sulfonic acid octadec-9-enyl-amide
• Peroxisome proliferator activated receptor alpha
• Proinflammatory cytokines
• Adhesion molecules
• Atherosclerosis

Our group synthesized propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator activated receptor alpha (PPAR alpha) agonist. Because PPAR alpha activation is associated with inflammation control, we hypothesize that N15 may have anti-inflammatory effects. We investigated the effect of N15 on the regulation of inflammation in THP-1cells stimulated with lipopolysaccharide (LPS). In particular, we assessed the production of chemokines, adhesion molecules and proinflammatory cytokines, three important types of cytokines that are released from monocytes and are involved in the development of atherosclerosis. The results showed that N15 remarkably reduced the mRNA expression of chemokines, such as monocyte chemotactic protein 1 (MCP-1 or CCL2), interleukin-8 (IL-8) and in terferon-inducible protein-10 (IP-10 or CXCL10), and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). N15 also decreased the protein expression of vascular cell adhesion molecule (VCAM) and matrix metalloproteinase(MMP) 2 and 9. The reduction in the expression of cytokine mRNAs observed following N15 treatment was abrogated in THP1 cells treated with PPAR alpha siRNA, indicating that the anti-inflammatory effects of N15 are dependent on PPAR alpha activation. Toll-liker eceptor 4 (TLR4)/nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription 3 (STAT3) inhibition, which are dependent on PPAR alpha activation, were also involved in the mechanism underlying the anti-inflammatory effects of N15. In conclusion, the novel PPAR alpha agonist, N15, exerts notable anti-inflammatory effects, which are mediated via PPAR alpha activation and TLR4/NF-kappa B and STAT3 inhibition, in LPS-stimulated THP-1cells. In our study, N15 exhibits promise for the treatment of atherosclerosis.

• 出版日期2016-10-5
• 单位厦门大学