Pseurotin D inhibits delayed type IV hypersensitivity response

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Authors

SKOROPLYAS Svitlana VAŠÍČEK Ondřej CHORVÁTOVÁ Michaela DAĎOVÁ Petra LEHKÁ Kateřina KUBALA Lukáš

Year of publication 2022
Type Article in Periodical
Magazine / Source Chemico-Biological Interactions
MU Faculty or unit

Faculty of Science

Citation
Web https://doi.org/10.1016/j.cbi.2022.110241
Doi http://dx.doi.org/10.1016/j.cbi.2022.110241
Keywords Pseurotin; Allergic response; Hypersensitivity; T cell; B cell
Description Pseurotins, secondary metabolites of fungi, represent a group of bioactive natural products with newly recognized biological activities, including the modulation of specific immune response. However, the type of immune response affected by pseurotins and the mechanistic details underlying these effects are still not understood. Thus, the aim of the current study was to examine the effects of pseurotin D on delayed-type IV hypersensitivity (DTH) reaction induced by chicken ovalbumin in vivo and to examine the effects of pseurotin D on major types of leukocytes responsible for DTH development in vitro. Pseurotin D significantly decreased paw swelling, the major symptom of DTH, as well as the DTH-related production of pro-inflammatory cytokine IL-1 beta, IL-4, IL-6, IFN-gamma and anti-inflammatory cytokine IL-10 in paws tissue, spleen enlargement, and DTH-related changes in leukocyte counts in peripheral blood. In vitro, pseurotin D mediated a decrease in the proliferation and differentiation of both Th1 and Th2 cells, as was concluded on the basis of the inhibition of the gene expressions of Gata3 and Tbx21 and the production of effector cytokines IFN-gamma and IL-13 in vitro. Further, pseurotin D significantly inhibited the activation and differentiation of B cells, as was documented by the significant inhibition of B cell proliferation, CD138 expression, and IgE production. In conclusion, the results show the potential of pseurotin D to inhibit DTH reaction, this phenomenon involving the inhibition of the activation and differentiation of both T cells and B cells.
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