Cigarette smoke attenuates mesenchymal stem cell-based suppression of immune cell-driven acute liver failure

Toxicol Lett. 2023 Aug 10:S0378-4274(23)00242-4. doi: 10.1016/j.toxlet.2023.08.006. Online ahead of print.ABSTRACTDetrimental effects of smoking on mesenchymal stem cell (MSC)-dependent immunosuppression and hepatoprotection are unknown. Herewith, by using α-galactosylceramide (α-GalCer)-induced liver injury, a well-established murine model of fulminant hepatitis, we examined molecular mechanisms which were responsible for negative effects of cigarette smoke on MSC-dependent immunomodulation. MSC which were grown in cigarette smoke-exposed medium (MSCWS-CM) obtained pro-inflammatory phenotype, were not able to optimally produce hepatoprotective and immunosuppressive cytokines (TGF-β, HGF, IL-10, NO, KYN), and secreted significantly higher amounts of inflammatory cytokines (IFN-γ, TNF-α, IL-17, IL-6) than MSC that were cultured in standard medium never exposed to cigarette smoke (MSCCM). In contrast to MSCCM, which efficiently attenuated α-GalCer-induced hepatitis, MSCWS-CM were not able to prevent hepatocyte injury and liver inflammation. MSCWS-CM had reduced capacity for the suppression of liver-infiltrated inflammatory macrophages, dendritic cells (DCs) and lymphocytes. Although significantly lower number of IL-12-producing macrophages and DCs, TNF-α, IFN-γ or IL-17-producing CD4+ and CD8+T lymphocytes, NK and NKT cells were noticed in the livers of α-GalCer+MSCCM-treated mice compared to α-GalCer+saline-treated animals, this phenomenon was not observed in α-GalC...

Source: Toxicology Letters - August 12, 2023 Category: Toxicology Authors: Dragica Pavlovic Dragana Miloradovic Milica Dimitrijevic Stojanovic Carl Randall Harrell Riccardo Polosa Sonja Rust Giovanni Li Volti Massimo Caruso Vladimir Jakovljevic Valentin Djonov Vladislav Volarevic Source Type: research