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cc-by (c) Pedrazza, Leonardo et al., 2017
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/124149

Mesenchymal stem cells decrease lung inflammation during sepsis, acting through inhibition of the MAPK pathway

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Background: Sepsis is a severe medical condition that ranks among the top 10 causes of death worldwide and which has permanently high incidence rates. Mesenchymal stem cells (MSCs) have been found to be potent modulators of immune responses. More importantly, there is evidence that MSCs have a beneficial effect on preclinical models of polymicrobial sepsis. However, the changes caused by the MSCs in the effector cells of the host immune system remain unclear. Methods: A mouse model of sepsis (male C57BL/6 mice) with three experimental groups was used for experiments in vivo: a control group, an untreated septic group, and a septic group treated with MSCs. In vitro experiments were performed using a cell line of pulmonary macrophages (RAW 264.7) co-cultured with MSCs and stimulated with lipopolysaccharide (LPS). Results: In vivo we demonstrated that treatment with MSCs was able to reduce the expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB), and thereby decrease the production of inflammatory cytokines. In vitro experiments using a co-culture of macrophages with MSCs showed a decrease in COX-2 and NF-κB, and showed that this reduction was directly related to the ability of MSCs to inhibit phosphorylation of ERK, RSK, and p38, enzymes that belong to the family of mitogen-activated protein kinases (MAPKs). Conclusions: This study demonstrated that MSCs are able to inhibit the MAPK pathway activation, modulating the inflammatory response during sepsis. This understanding that MSCs can remodel the response of host cells and improve the course of sepsis is essential for developing new treatments for this pathology.

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PEDRAZZA, Leonardo, CUBILLOS ROJAS, Mónica, MESQUITA, Fernanda cristina de, LUFT, Carolina, CUNHA, Aline andrea, ROSA LÓPEZ, José luis, RODRIGUES DE OLIVEIRA, Jarbas. Mesenchymal stem cells decrease lung inflammation during sepsis, acting through inhibition of the MAPK pathway. _Stem Cell Research & Therapy_. 2017. Vol. 8, núm. 289. [consulta: 20 de gener de 2026]. ISSN: 1757-6512. [Disponible a: https://hdl.handle.net/2445/124149]

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