Treatment with Apocynin Limits the Development of Acute Graft-versus-Host Disease in Mice

Autor: Vanessa Pinho, Mauro M. Teixeira, Bárbara M. Rezende, Marina G. M. Castor, Carolina Braga de Resende, Rayssa Maciel Athayde, Thiago Vinícius Ávila, William Antonio Gonçalves, Priscila T. T. Bernardes, Débora Gonzaga Martins
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
lcsh:Immunologic diseases. Allergy
Chemokine
Article Subject
medicine.medical_treatment
Immunology
Graft vs Host Disease
Hematopoietic stem cell transplantation
medicine.disease_cause
Proinflammatory cytokine
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Immunology and Allergy
Medicine
Animals
Transplantation
Homologous
Transplantation Chimera
NADPH oxidase
biology
business.industry
Macrophages
Hematopoietic Stem Cell Transplantation
Acetophenones
NADPH Oxidases
General Medicine
Transplantation
Oxidative Stress
030104 developmental biology
surgical procedures
operative
chemistry
Liver
030220 oncology & carcinogenesis
Apocynin
biology.protein
Increased inflammatory response
Cytokines
business
lcsh:RC581-607
Reactive Oxygen Species
Oxidative stress
Immunosuppressive Agents
Research Article
Zdroj: Journal of Immunology Research
Journal of Immunology Research, Vol 2019 (2019)
ISSN: 2314-8861
DOI: 10.1155/2019/9015292
Popis: Graft-versus-host disease (GVHD) is the most serious complication limiting the clinical utility of allogeneic hematopoietic stem cell transplantation (HSCT), in which lymphocytes of donors (graft) are activated in response to the host antigen. This disease is associated with increased inflammatory response through the release of inflammatory mediators such as cytokines, chemokines, and reactive oxygen species (ROS). In this study, we have evaluated the role of ROS in GVHD pathogenesis by treatment of recipient mice with apocynin (apo), an inhibitor of intracellular translocation of cytosolic components of NADPH oxidase complex. The pharmacological blockade of NADPH oxidase resulted in prolonged survival and reduced GVHD clinical score. This reduction in GVHD was associated with reduced levels of ROS and TBARS in target organs of GVHD in apocynin-treated mice at the onset of the mortality phase. These results correlated with reduced intestinal and liver injuries and decreased levels of proinflammatory cytokines and chemokines. Mechanistically, pharmacological blockade of the NADPH oxidase was associated with inhibition of recruitment and accumulation of leukocytes in the target organs. Additionally, the chimerism remained unaffected after treatment with apocynin. Our study demonstrates that ROS plays an important role in mediating GVHD, suggesting that strategies aimed at blocking ROS production may be useful as an adjuvant therapy in patients subjected to bone marrow transplantation.
Databáze: OpenAIRE
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