Growth arrest-specific gene 6 administration ameliorates sepsis-induced organ damage in mice and reduces ros formation in vitro

Livia Salmi, Francesco Gavelli, Filippo Patrucco, Mattia Bellan, Pier Paolo Sainaghi, Gian Carlo Avanzi, Luigi Mario Castello

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Sepsis is a widespread life-threatening disease, with a high mortality rate due to inflammation-induced multiorgan failure (MOF). Thus, new effective modulators of the immune response are urgently needed to ameliorate the outcome of septic patients. As growth arrest-specific gene 6 (Gas6)/Tyro3, Axl, MerTK (TAM) receptors signaling has shown immunomodulatory activity in sepsis, here we sought to determine whether Gas6 protein injection could mitigate MOF in a cecal slurry mouse model of sepsis. Mice, divided into different groups according to treatment—i.e., placebo (B), ampicillin (BA), Gas6 alone (BG), and ampicillin plus Gas6 (BAG)—were assessed for vitality, histopathology and cytokine expression profile as well as inducible nitric oxide synthase (iNOS), ALT and LDH levels. BAG-treated mice displayed milder kidney and lung damage and reduced levels of cytokine expression and iNOS in the lungs compared to BA-treated mice. Notably, BAG-treated mice showed lower LDH levels compared to controls. Lastly, BAG-treated cells of dendritic, endothelial or monocytic origin displayed reduced ROS formation and increased cell viability, with a marked upregulation of mitochondrial activity. Altogether, our findings indicate that combined treatment with Gas6 and antibiotics ameliorates sepsis-induced organ damage and reduces systemic LDH levels in mice, suggesting that Gas6 intravenous injection may be a viable therapeutic option in sepsis.

Lingua originaleInglese
Numero di articolo602
pagine (da-a)1-15
Numero di pagine15
RivistaCells
Volume10
Numero di pubblicazione3
DOI
Stato di pubblicazionePubblicato - mar 2021

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