Immunomodulatory potential of bioactive plant substances in the inflammasome activation and polarization of M1 and M2 macrophage subsets

Abstract

The search for new drugs is a constant in modern society, in view of both existence of diseases that have no further treatment and the need for more potent drugs and / or with less side effects, than those already known. Recently, our laboratory has began studies evaluating the effect of bioactive plant substances in this context. Using cultured human monocytes challenged with lipopolysaccharide (LPS), we observed crude extracts from species of the genus Piper, Peperomia, Eugenia and Davilla interfere in the production of pro-inflammatory cytokines, sometimes increasing or reducing their release. These results suggest that these substances may act by altering the phenotypes of M1 and M2 macrophage subsets. Similarly, some of the extracts induced decrease in the production of IL-1², showing interference in the inflammasome activation. Whereas both activation of the inflammasome and polarization of macrophages are key elements in the pathogenesis and development of inflammatory diseases, this study aims to study the immunomodulatory potential of crude extracts, fractions, and / or substances isolated from the species of Piper, Peperomia, Eugenia and Davilla. To study the effects on NLRP3 inflammasome, THP-1 monocyte lineage will be challenged with LPS, ATP, inhibitors and/or bioactive substances. Then, production of IL-1² and expression of intracellular NLRP3, ASC, caspase-1, pro-IL1², IL1-², pro-IL18 and IL-18 will be evaluated. To evaluate the effects of the substances on macrophage polarization, macrophages derived from human monocytes and polarized in M1 and M2 will be challenged with bioactive substances. Macrophage activity will be evaluated by production of hydrogen peroxide, IL-10, TNF-±, IL-6, PGE-2, IL-1², IL-18 and IL-8 and by expression of MHC-II, MR, TLR-2, TLR-4, CD40 and CD86. (AU)