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Javamide-II Inhibits IL-6 without Significant Impact on TNF-alpha and IL-1beta in Macrophage-Like Cells

Diet, Genomics, and Immunology Laboratory, Bldg. 307C, Rm. 131, BHNRC, ARS, USDA, Beltsville, MD 20705, USA
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Biomedicines 2020, 8(6), 138; https://doi.org/10.3390/biomedicines8060138
Received: 3 May 2020 / Revised: 24 May 2020 / Accepted: 27 May 2020 / Published: 29 May 2020
(This article belongs to the Special Issue The Interleukin-6 Family in Disease Pathogenesis and Therapy)
The main aim of this study is to find a therapeutic compound to inhibit IL-6, not TNF-alpha and IL-1beta, in macrophage-like cells, because the high-levels of IL-6 production by macrophages are reported to cause unfavorable outcomes under several disease conditions (e.g., autoimmune diseases, and acute viral infections, including COVID-19). In this study, the potential effects of javamide-II on IL-6, IL-1beta and TNF-alpha productions were determined using their ELISA kits in macrophage-like THP-1 cells. Western blots were also performed using the same cells, to determine its effects on signaling pathways (ERK, p38, JNK, c-Fos, ATF-2, c-Jun and NF-κB p65). At concentrations of 0.2–40 µM, javamide-II inhibited IL-6 production significantly in the THP-1 cells (IC50 of 0.8 µM) (P < 0.02). However, javamide-II did not inhibit IL-1beta or TNF-alpha productions much at the same concentrations. In addition, the treatment of javamide-II decreased the phosphorylation of p38 without significant effects on ERK and JNK phosphorylations in the THP-1 cells. Furthermore, the p38 inhibition, followed by the reduction of ATF-2 phosphorylation (not c-Fos, c-Jun or NF-κB p65), led to the suppression of IL-6 mRNA expression in the cells (P < 0.02). The data indicate that javamide-II may be a potent compound to inhibit IL-6 production via suppressing the p38 signal pathway, without significant effects on the productions of TNF-alpha and IL-1beta in macrophage-like THP-1 cells. View Full-Text
Keywords: Javamide-II (N-caffeoyltryptophan); Infection; COVID-19; IL-6 inhibition; p38/ATF-2; macrophage-like THP-1 cells Javamide-II (N-caffeoyltryptophan); Infection; COVID-19; IL-6 inhibition; p38/ATF-2; macrophage-like THP-1 cells
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Park, J.B.; Peters, R.; Pham, Q.; Wang, T.T.Y. Javamide-II Inhibits IL-6 without Significant Impact on TNF-alpha and IL-1beta in Macrophage-Like Cells. Biomedicines 2020, 8, 138.

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