%0 Figure %A Limongi, Dolores %A Baldelli, Sara %A Checconi, Paola %A Marcocci, Mariaelena %A De Chiara, Giovanna %A Fraternale, Alessandra %A Magnani, Mauro %A Ciriolo, Maria Rosa %A Palamara, Anna Teresa %D 2019 %T Image_2_GSH-C4 Acts as Anti-inflammatory Drug in Different Models of Canonical and Cell Autonomous Inflammation Through NFκB Inhibition.tif %U https://frontiersin.figshare.com/articles/figure/Image_2_GSH-C4_Acts_as_Anti-inflammatory_Drug_in_Different_Models_of_Canonical_and_Cell_Autonomous_Inflammation_Through_NF_B_Inhibition_tif/7678901 %R 10.3389/fimmu.2019.00155.s002 %2 https://frontiersin.figshare.com/ndownloader/files/14274635 %K glutathione %K macrophage %K adipocytes %K myocytes %K cytokine %X

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.

%I Frontiers