Natural pseurotins and analogs thereof inhibit activation of B-cells and differentiation into the plasma cells

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
Ondřej VašíčekLukáš Kubala

Abstract

The frequency of allergic diseases is constantly rising. Dysregulated production of isotype E immunoglobulins is one of the key factors behind allergic reactions and its modulation is therefore an important target for pharmacological intervention. Natural products of the pseurotin family were reported to be inhibitors of IgE production in B-cells. Mechanistic details underlying these effects are however not well understood. In the present study, we synthesized new analogs of natural pseurotins and extensively investigated their inhibitory effects on activation, proliferation and differentiation of B-cells, as well as on the production of IgE. Effects of two natural pseurotins (pseurotins A and D) and a collection of fully synthetic pseurotin analogs were studied on mouse B-cells stimulated by the combination of IL-4 and E. coli lipopolysaccharide. The IgE production was determined along with cell viability and cell proliferation. The phosphorylation of selected members of the STAT transcription factor family was subsequently investigated. Finally, the in vivo effect of pseurotin D on the ovalbumin-induced delayed type hypersensitivity response was tested in mice. We discovered that several fully synthetic pseurotin analogs were...Continue Reading

Citations

Mar 7, 2021·International Journal of Molecular Sciences·Daniela RubanovaLukas Kubala

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