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

Dolores Limongi, Sara Baldelli, Paola Checconi, Maria Elena Marcocci, Giovanna De Chiara, Alessandra Fraternale, Mauro Magnani, Maria Rosa Ciriolo, Anna Teresa Palamara

Research output: Contribution to journalArticle

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-C4 can be envisaged as a good candidate to abrogate such process, expanding the anti-inflammatory role of this molecule in chronic inflammatory states.

Original languageEnglish
Pages (from-to)155
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 2019

Keywords

  • Adipocytes/drug effects
  • Animals
  • Anti-Inflammatory Agents/pharmacology
  • Cells, Cultured
  • Cytokines/metabolism
  • Glutathione/analogs & derivatives
  • Humans
  • Lipopolysaccharides/pharmacology
  • Macrophages/drug effects
  • Muscle Fibers, Skeletal/drug effects
  • NF-kappa B/antagonists & inhibitors

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