GSH-C4 Acts as Anti-inflammatory Drug in Different Models of Canonical and Cell Autonomous Inflammation Through NFκB Inhibition

Frontiers in Immunology
Dolores LimongiAnna Teresa Palamara

Abstract

An imbalance in GSH/GSSG ratio represents a triggering event in pro-inflammatory cytokine production and inflammatory response. However, the molecular mechanism(s) through which GSH regulates macrophage and cell autonomous inflammation remains not deeply understood. Here, we investigated the effects of a derivative of GSH, the N-butanoyl glutathione (GSH-C4), a cell permeable compound, on lipopolisaccharide (LPS)-stimulated murine RAW 264.7 macrophages, and human macrophages. LPS alone induces a significant production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α and a significant decrement of GSH content. Such events were significantly abrogated by treatment with GSH-C4. Moreover, GSH-C4 was highly efficient in buffering cell autonomous inflammatory status of aged C2C12 myotubes and 3T3-L1 adipocytes by suppressing the production of pro-inflammatory cytokines. We found that inflammation was paralleled by a strong induction of the phosphorylated form of NFκB, which translocates into the nucleus; a process that was also efficiently inhibited by the treatment with GSH-C4. Overall, the evidence suggests that GSH decrement is required for efficient activation of an inflammatory condition and, at the same time, GSH-C...Continue Reading

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Citations

Jul 22, 2020·BMC Microbiology·Ker-Kong ChenKazunari K Yokoyama
Apr 3, 2020·Antioxidants·Valentina Di PietroAngela Maria Amorini
Aug 28, 2020·International Journal of Antimicrobial Agents·Alessandra FraternaleGiuditta Fiorella Schiavano
Apr 4, 2021·International Journal of Molecular Sciences·Alessandra FraternaleRita Crinelli
Oct 1, 2020·Antioxidants·Vika GuloyanVishwanath Venketaraman

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Methods Mentioned

BETA
nuclear translocation
ChIP
immunoprecipitation
Assay
light microscopy
FCS

Software Mentioned

Genomatix Software Suite

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