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Retinoic Acid-Induced Regulation of Inflammatory Pathways Is a Potential Sepsis Treatment.
Dolin, Hallie H; Franco, Justin H; Chen, Xiaohuan; Pan, Zhixing K.
Afiliación
  • Dolin HH; Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
  • Franco JH; Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
  • Chen X; Department of Neuroscience, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
  • Pan ZK; Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA.
Infect Immun ; 91(4): e0045722, 2023 04 18.
Article en En | MEDLINE | ID: mdl-36877073
Sepsis is among the most dangerous known diseases, resulting from the dysregulation of the innate immune system in a process that is characterized largely by proinflammatory cytokines. It manifests as an excessive immune response to a pathogen and often leads to life-threatening complications such as shock and multiple-organ failure. Within the past several decades, much progress has been made to better understand the pathophysiology of sepsis and improve treatment. However, the average case-fatality rate for sepsis remains high. Current anti-inflammatory therapeutics for sepsis are not effective for use as first-line treatments. Focusing on all-trans-retinoic acid (RA), or activated vitamin A, as a novel anti-inflammatory agent, we have shown both in vitro and in vivo that RA decreases the production of proinflammatory cytokines. In vitro studies using mouse RAW 264.7 macrophages show that RA decreases tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß) and increases mitogen-activated protein kinase phosphatase 1 (MKP-1). RA treatment was also associated with the reduced phosphorylation of key inflammatory signaling proteins. Using a lipopolysaccharide and cecal slurry sepsis model, we found that RA significantly reduced mortality rates in mice, downregulated proinflammatory cytokine production, decreased neutrophil infiltration into lung tissue, and reduced the destructive lung histopathology typically seen in sepsis. We propose that RA may increase the function of native regulatory pathways and serve as a novel treatment for sepsis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tretinoina / Sepsis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tretinoina / Sepsis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos