NO-IL-6/10-IL-1β axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor rats

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:33:24Z
Fecha de publicación2023-01-01
ResumenIntroductionBrain death (BD) and steatosis are both risk factors for organ dysfunction or failure in liver transplantation (LT) Material and methodsHere, we examine the role of interleukin 6 (IL- 6) and IL-10 in LT of both non-steatotic and steatotic liver recovered from donors after brain death (DBDs), as well as the molecular signaling pathways underlying the effects of such cytokines. ResultsBD reduced IL-6 levels only in nonsteatotic grafts, and diminished IL-10 levels only in steatotic ones. In both graft types, BD increased IL-1 \& beta;, which was associated with hepatic inflammation and damage. IL-6 administration reduced IL-1 \& beta; only in non-steatotic grafts and protected them against damage and inflammation. Concordantly, IL-1 \& beta; inhibition via treatment with an IL-1 receptor antagonist caused the same benefits in non-steatotic grafts. Treatment with IL-10 decreased IL-1 \& beta; only in steatotic grafts and reduced injury and inflammation specifically in this graft type. Blockading the IL-1 \& beta; effects also reduced damage and inflammation in steatotic grafts. Also, blockade of IL-1 \& beta; action diminished hepatic cAMP in both types of livers, and this was associated with a reduction in liver injury and inflammation, then pointing to IL-1 \& beta; regulating cAMP generation under LT and BD conditions. Additionally, the involvement of nitric oxide (NO) in the effects of interleukins was evaluated. Pharmacological inhibition of NO in LT from DBDs prompted even more evident reductions of IL-6 or IL-10 in non-steatotic and steatotic grafts, respectively. This exacerbated the already high levels of IL-1 \& beta; seen in LT from DBDs, causing worse damage and inflammation in both graft types. The administration of NO donors to non-steatotic grafts potentiated the beneficial effects of endogenous NO, since it increased IL-6 levels, and reduced IL-1 \& beta;, inflammation, and damage. However, treatment with NO donors in steatotic grafts did not modify IL-10 or IL-1 \& beta; levels, but induced more injurious effects tan the induction of BD alone, characterized by increased nitrotyrosine, lipid peroxidation, inflammation, and hepatic damage. ConclusionOur study thus highlights the specificity of new signaling pathways in LT from DBDs: NO-IL-6-IL-1 \& beta; in non-steatotic livers and NO-IL-10-IL-1 \& beta; in steatotic ones. This opens up new therapeutic targets that could be useful in clinical LT.es_ES
Doihttps://doi.org/10.3389/fimmu.2023.1178909es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/5213
Idiomaenes_ES
EditorialFRONTIERS MEDIA SAes_ES
RelaciónFrontiers in Immunologyes_ES
URL relacionadohttps://doi.org/10.3389/fimmu.2023.1178909es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteFrontiers in Immunology
Palabra clavebrain deathes_ES
Palabra claveliver transplantationes_ES
Palabra clavenitric oxidees_ES
Palabra clavesteatotic liver graftses_ES
Palabra claveIL-10es_ES
Palabra claveIL-6es_ES
Palabra claveIL-1es_ES
Palabra claveischemia-reperfusiones_ES
TítuloNO-IL-6/10-IL-1β axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor ratses_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorCasillas-Ramirez, Arani
AutorMico-Carnero, Marc
AutorSanchez-Gonzalez, Alfredo
AutorMaroto-Serrat, Cristina
AutorTrostchansky, Andres
AutorPeralta, Carmen
AutorCasillas-Ramirez, Aranies_ES
AutorMico-Carnero, Marces_ES
AutorSanchez-Gonzalez, Alfredoes_ES
AutorMaroto-Serrat, Cristinaes_ES
AutorTrostchansky, Andreses_ES
AutorPeralta, Carmenes_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
URL relacionadahttps://doi.org/10.3389/fimmu.2023.1178909
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen14es_ES

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