Fluvastatin Suppresses Mast Cell and Basophil IgE Responses: Genotype-Dependent Effects

The Journal of Immunology : Official Journal of the American Association of Immunologists
Elizabeth Motunrayo KolawoleJohn J Ryan

Abstract

Mast cell (MC)- and basophil-associated inflammatory diseases are a considerable burden to society. A significant portion of patients have symptoms despite standard-of-care therapy. Statins, used to lower serum cholesterol, have immune-modulating activities. We tested the in vitro and in vivo effects of statins on IgE-mediated MC and basophil activation. Fluvastatin showed the most significant inhibitory effects of the six statins tested, suppressing IgE-induced cytokine secretion among mouse MCs and basophils. The effects of fluvastatin were reversed by mevalonic acid or geranylgeranyl pyrophosphatase, and mimicked by geranylgeranyl transferase inhibition. Fluvastatin selectively suppressed key FcεRI signaling pathways, including Akt and ERK. Although MCs and basophils from the C57BL/6J mouse strain were responsive to fluvastatin, those from 129/SvImJ mice were completely resistant. Resistance correlated with fluvastatin-induced upregulation of the statin target HMG-CoA reductase. Human MC cultures from eight donors showed a wide range of fluvastatin responsiveness. These data demonstrate that fluvastatin is a potent suppressor of IgE-mediated MC activation, acting at least partly via blockade of geranyl lipid production downs...Continue Reading

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Citations

Jan 8, 2019·Journal of Biomedical Materials Research. Part a·Daniel AbebayehuJohn J Ryan
Nov 4, 2016·International Forum of Allergy & Rhinology·Eun Jung LeeKyung-Su Kim
May 28, 2020·Current Atherosclerosis Reports·Hamideh KouhpeikarAmirhossein Sahebkar
May 15, 2018·Frontiers in Immunology·Heather L CaslinJohn J Ryan
Oct 26, 2018·Circulation·Giampaolo NiccoliFilippo Crea
May 22, 2020·The Journal of Pharmacology and Experimental Therapeutics·Patrick A PaezJohn J Ryan
Jun 26, 2020·Frontiers in Pharmacology·Piero Sestili, Vilberto Stocchi
Apr 30, 2019·Cellular Immunology·Daniel AbebayehuSydney Ann Kee

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