Inhibition of interleukin-8 production in interleukin-1 stimulated human monocytic THP-1 cells by N,N didesmethylgrossularine-1 obtained from an Ascidian Polycarpa aurata collected in North Sulawesi

3rd Indonesian Operations Research Association - International Conference on Operations Research 2018

计算机科学

Sumilat, D.A.^1 ; Oda, T.^2 ; Wewengkang, D.S.^3 ; Namikoshi, M.^4 ; Yamazaki, H.^4

Faculty of Fisheries and Marine Science, Sam Ratulangi University, Indonesia^1

Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, Japan^2

Faculty of Mathematic and Natural Sciences, Sam Ratulangi University, Indonesia^3

Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Japan^4

关键词: Active components;    Drug candidates;    Inflammatory cytokines;    Inhibitory activity;    Interleukin-8;    Raw 264.7 cells;    Signalling pathways;    Tumor necrosis factors;   

Others  :  https://iopscience.iop.org/article/10.1088/1757-899X/567/1/012021/pdf
DOI  :  10.1088/1757-899X/567/1/012021

学科分类：计算机科学（综合）

来源: IOP

【 摘 要 】

N,N-Didesmethylgrossularine-1 (DDMG-1) has a rare β-carboline structure and was isolated from an Indonesian ascidian Polycarpa aurata as an active component against tumor necrosis factor (TNF)α production in lipopolysaccharine (LPS)-stimulated murine macrophase-like RAW 264.7 cells as reported in our previous paper. Further investigation on the inhibitory activity of DDMG-1 against the production of inflammatory cytokines in human monocytic THP-1 cells, we found that DDMG-1 reduced the excess production of IL-8 in LPS- stimulated THP-1 cells through inhibition of the mRNA level of IL-8 1κB-α degradation, and binding of NF-xfi to the target DNA site. The THP-1 cells used in this study showed the high production of IL-8 by the stimulation with TNF-α, IL-1β, and 12-O-tetradecanoylphorbol-13-acetate (PMA) as similar to LPS. DDMG-1 inhibited the IL-8 production in IL-1β-stimulated THP-1 cells but did not show an inhibitory activity in the cells stimulated by TNF-α and PMA. Therefore, DDMG-1 was specific to the IL-1β signalling pathway. These results suggested that DDMG-1 could be a useful drug candidate lead compound to control the excess production of IL-8.