The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory parasitic worm product, ES-62

Immunology Letters
Kara S BellWilliam Harnett

Abstract

ES-62, a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae, has been shown to modulate the immune system through subversion of signal transduction pathways operating in various immune system cells. With respect to human bone marrow-derived mast cells (BMMCs), ES-62 was previously shown to inhibit FcϵRI-mediated mast cell functional responses such as degranulation and pro-inflammatory cytokine release through a mechanism involving the degradation of PKC-α. At the same time, it was noted that the worm product was able to degrade certain other PKC isoforms but the significance of this was uncertain. In this study, we have employed PKC isoform KO mice to investigate the role of PKC-α, -β -ϵ, and -θ in mouse BMMCs in order to establish their involvement in mast cell-mediated responses and also, if their absence impacts on ES-62's activity. The data obtained support that in response to antigen cross-linking of IgE bound to FcϵRI, pro-inflammatory cytokine release is controlled in part by a partnership between one conventional and one novel isoform with PKC-α and -θ acting as positive regulators of IL-6 and TNF-α production, while PKC-β and ϵ act as negative regulators of such cytokines. Furthermore, ES-62 appear...Continue Reading

References

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Citations

Mar 1, 2016·Frontiers in Immunology·Arkajyoti MukherjeeDebasri Mukherjee
Sep 25, 2018·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Michael S BalzerNelli Shushakova
Jul 18, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Phil-Dong MoonHyun-Ja Jeong
Oct 30, 2018·Frontiers in Immunology·Amin ZakeriPeter Nejsum
Oct 30, 2020·Journal of Asthma and Allergy·Birhanu AyelignTewodros Shibabaw
Jun 20, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Na-Ra HanHi-Joon Park
Jun 21, 2021·International Journal of Biological Macromolecules·Emilio M Serrano-LópezSenena Corbalán-García

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Methods Mentioned

BETA
FACS
flow cytometry
ELISAs
ELISA
Assay
electrophoresis
protein assay

Software Mentioned

Graphpad PRISM
Flowjo

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