We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Growth Arrest-Specific Gene 6 Administration Ameliorates Sepsis-Induced Organ Damage in Mice and Reduces ROS Formation In Vitro.
- Authors
Salmi, Livia; Gavelli, Francesco; Patrucco, Filippo; Bellan, Mattia; Sainaghi, Pier Paolo; Avanzi, Gian Carlo; Castello, Luigi Mario; Frutos, Pablo García De
- 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.
- Subjects
NITRIC-oxide synthases; MICE; INTRAVENOUS injections; MULTIPLE organ failure; INJECTIONS; CYTOKINES
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 3, p602
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10030602