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Corticosteroids protect infected cells against mycobacterial killing in vitro
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).ORCID iD: 0000-0002-2259-6883
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
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2019 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 511, no 1, p. 117-121Article in journal (Refereed) Published
Abstract [en]

The effect of corticosteroids on human physiology is complex and their use in tuberculosis patients remains controversial. In a high-throughput screening approach designed to discover virulence inhibitors, several corticosteroids were found to prevent cytolysis of fibroblasts infected with mycobacteria. Further experiments with Mycobacterium tuberculosis showed anti-cytolytic activity in the 10 nM range, but no effect on bacterial growth or survival in the absence of host cells at 20 mu M. The results from a panel of corticosteroids with various affinities to the glucocorticoid- and mineralocorticoid receptors indicate that the inhibition of cytolysis most likely is mediated through the glucocorticoid receptor. Using live-imaging of M. tuberculosis-infected human monocyte-derived macrophages, we also show that corticosteroids to some extent control intracellular bacteria. In vitro systems with reduced complexity are to further study and understand the interactions between bacterial infection, immune defense and cell signaling. (C) 2019 The Authors. Published by Elsevier Inc.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2019. Vol. 511, no 1, p. 117-121
Keywords [en]
Mycobacterium, Tuberculosis, Corticosteroids, Cell death, Drug discovery
National Category
Immunology
Identifiers
URN: urn:nbn:se:umu:diva-157508DOI: 10.1016/j.bbrc.2019.02.044ISI: 000460849800019PubMedID: 30773257OAI: oai:DiVA.org:umu-157508DiVA, id: diva2:1302614
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-05Bibliographically approved

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Tükenmez, HasanEdström, IsabelLindberg, StinaSundin, CharlottaElofsson, Mikael

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Tükenmez, HasanEdström, IsabelLindberg, StinaSundin, CharlottaElofsson, Mikael
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