Open AccessInhibition 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
Author(s) -
Deiske A. Sumilat,
Taiko Oda,
Defny S. Wewengkang,
Michio Namikoshi,
Hiromi Yamazaki
Publication year - 2019
Publication title -
iop conference series. materials science and engineering
Language(s) - English
Resource type - Journals
eISSN - 1757-899X
pISSN - 1757-8981
DOI - 10.1088/1757-899x/567/1/012021
Subject(s) - thp1 cell line , tumor necrosis factor alpha , stimulation , microbiology and biotechnology , interleukin , biology , interleukin 6 , cell culture , cytokine , immunology , endocrinology , genetics
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.