Fluvastatin enhances IL-33-mediated mast cell IL-6 and TNF production.

Autor: Taruselli MT; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, United States., Kolawole EM; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States., Qayum AA; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, United States., Haque TT; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, United States., Caslin HL; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States., Abebayehu D; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23298, United States., Kee SA; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States., Dailey JM; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, United States., Jackson KG; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, United States., Burchett JR; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, United States., Spence AJ; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States., Pondicherry N; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States., Barnstein BO; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States., Gomez G; University of Houston College of Medicine, Department of Biomedical Sciences, Houston, TX 77204, United States., Straus DB; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States., Ryan JJ; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, United States. Electronic address: jjryan@vcu.edu.
Jazyk: angličtina
Zdroj: Cellular immunology [Cell Immunol] 2022 Jan; Vol. 371, pp. 104457. Date of Electronic Publication: 2021 Nov 24.
DOI: 10.1016/j.cellimm.2021.104457
Abstrakt: Statins are HMG-CoA reductase inhibitors prescribed for lowering cholesterol. They can also inhibit inflammatory responses by suppressing isoprenylation of small G proteins. Consistent with this, we previously found that fluvastatin suppresses IgE-mediated mast cell function. However, some studies have found that statins induced pro-inflammatory cytokines in macrophages and NK cells. In contrast to IgE signaling, we show that fluvastatin augments IL-33-induced TNF and IL-6 production by mast cells. This effect required the key mast cell growth factor, stem cell factor (SCF). Treatment of IL-33-activated mast cells with mevalonic acid or isoprenoids reduced fluvastatin effects, suggesting fluvastatin acts at least partly by reducing isoprenoid production. Fluvastatin also enhanced IL-33-induced NF-κB transcriptional activity and promoted neutrophilic peritonitis in vivo, a response requiring mast cell activation. Other statins tested did not enhance IL-33 responsiveness. Therefore, this work supports observations of unexpected pro-inflammatory effects of some statins and suggests mechanisms by which this may occur. Because statins are candidates for repurposing in inflammatory disorders, our work emphasizes the importance of understanding the pleiotropic and possible unexpected effects of these drugs.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: