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

Frontiers in Immunology

Sara Baldelli²  Paola Checconi²  Dolores Limongi²  Maria Elena Marcocci³  Maria Rosa Ciriolo⁴  Anna Teresa Palamara⁵  Giovanna De Chiara⁶  Mauro Magnani⁷  Alessandra Fraternale⁷ 

[1] Department of Biology, University of Rome “Tor Vergata”, Rome, Italy;Department of Human Sciences and Promotion of the Quality of Life, IRCCS San Raffaele Pisana, San Raffaele Roma Open University, Rome, Italy;Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy;IRCCS San Raffaele Pisana, Rome, Italy;Institute Pasteur-Fondazione Cenci Bolognetti, Rome, Italy;Institute of Translational Pharmacology, National Research Council Rome, Rome, Italy;University of Urbino Carlo Bo, Department of Biomolecular Sciences, Urbino, Italy;

关键词: glutathione;    macrophage;    adipocytes;    myocytes;    cytokine;   

DOI  :  10.3389/fimmu.2019.00155

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown