Glutathione fine-tunes the innate immune response toward antiviral pathways in a macrophage cell line independently of its antioxidant properties

Diotallevi, Marina, Mengozzi, Manuela and Ghezzi, Pietro (2017) Glutathione fine-tunes the innate immune response toward antiviral pathways in a macrophage cell line independently of its antioxidant properties. Frontiers in Immunology. ISSN 1664-3224

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Abstract

Glutathione (GSH), a major cellular antioxidant, is considered an inhibitor of the inflammatory response involving reactive oxygen species (ROS). However, evidence is largely based on experiments with exogenously added antioxidants/reducing agents or pro-oxidants. We show that depleting macrophages of 99% of GSH does not exacerbate the inflammatory gene expression profile in the RAW264 macrophage cell line or increase expression of inflammatory cytokines in response to the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS); only two small patterns of LPS-induced genes were sensitive to GSH depletion. One group, mapping to innate immunity and antiviral responses (Oas2, Oas3, Mx2, Irf7, Irf9, STAT1, il1b), required GSH for optimal induction. Consequently, GSH depletion prevented the LPS-induced activation of antiviral response and its inhibition of influenza virus infection. LPS induction of a second group of genes (Prdx1, Srxn1, Hmox1, GSH synthase, cysteine transporters), mapping to nrf2 and the oxidative stress response, was increased by GSH depletion. We conclude that the main function of endogenous GSH is not to limit inflammation but to fine-tune the innate immune response to infection.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: R Medicine
Related URLs:
Depositing User: Pietro Ghezzi
Date Deposited: 10 Oct 2017 12:41
Last Modified: 10 Oct 2017 12:41
URI: http://sro.sussex.ac.uk/id/eprint/70475

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