Javamide-II inhibits IL-6 without significant impact on TNF-alpha and IL-1beta in macrophage-like cells

Authors: Park, Jae; Peters, Renee; Pham, Quynhchi; Wang, Thomas - Tom

Submitted to: BioMedical Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2020
Publication Date: 5/29/2020
Citation: Park, J.B., Peters, R.C., Pham, Q., Wang, T.T. 2020. Javamide-II inhibits IL-6 without significant impact on TNF-alpha and IL-1beta in macrophage-like cells. BioMedical Journal. 8(6);138. https://doi.org/10.3390/biomedicines8060138.
DOI: https://doi.org/10.3390/biomedicines8060138

Interpretive Summary: Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine that plays crucial roles in not only the immune functions, but also a variety of biological processes such as metabolism, bone homeostasis and cognitive functions. A dysfunction of IL-6 regulation often leads to the progression of acute and chronic conditions in these diseases. Therefore, compounds to inhibit IL-6 have been sought out to attenuate pathological conditions of several IL-6 related diseases (e.g., chronic inflammation, autoimmune diseases and rheumatoid arthritis). Javamide-II is a phenolic amide found in coffee. Recently, javamide-II and its analogues were reported to have several biological activities including anti-inflammatory activity. However, there is no information about the effect of javamide-II on IL-6 expression. Therefore, in this paper, the potential effects of javamide-II on the expression of IL-6 cytokines were investigated in PMA-differentiated macrophage-like THP-1 cells. The data of thid study suggests that javamide-II may be a potent compound to inhibit IL-6 expression preferentially via suppressing p38/ATF-2 phosphorylation in PMA-differentiated THP-1 cells. Also, the data showed the inhibition of IL-6 may have little effect on the productions of IL-1beta and TNF-alpha in the same cells, suggesting that the compound may inhibit IL-6 expression in a way devoid of IL-1beta and TNF-alpha inhibitions. This study provided new information about javamide-II as a potential selective IL-6 inhibitor and its utility in attenuating pathological conditions in IL-6 related diseases.

Technical Abstract: IL-6 is an inflammatory cytokine, critically involved in the pathogenesis of several human diseases including diabetes, liver and autoimmune diseases. Recent reports suggest that coffee consumption may have positive health effects on several chronic diseases such as diabetes and liver disease. However, there is no information about the potential effects of javamide-II found in coffee on IL-6 expression in cells including macrophages. Therefore, in this paper, its effect on IL-6 expression was investigated in PMA-differentiated macrophage-like THP-1 cells. At concentrations of 0.5-40 µM, javamide-II inhibited IL-6 production significantly in the THP-1 cells (P < 0.05). However, at the same concentrations, javamide-II had little effect on the productions of IL-1beta and TNF-alpha in the same cells, suggesting that the compound may inhibit IL-6 expression in a way devoid of IL-1beta and TNF-alpha inhibitions. In addition, the treatment of javamide-II decreased the phosphorylation of p38 in the cells, although it had no significant effect on those of ERK and JNK. Furthermore, the inhibition of p38 phosphorylation was followed by the inhibition of ATF-2 phosphorylation, but not c-Fos, c-Jun or NF-kB p65 inhibition. However, the inhibition of p38/ATF-2 was found to be enough to suppress IL-6 mRNA expression in the cells (P < 0.05). In summary, javamide-II may be a potent compound to inhibit IL-6 expression preferentially via suppressing p38/ATF-2 phosphorylation in PMA-differentiated THP-1 cells.