Compound A Increases Cell Infiltration in Target Organs of Acute Graft-versus-Host Disease (aGVHD) in a Mouse Model

Bouazzaoui, Abdellatif and Abdellatif, Ahmed A. H. and Al-Allaf, Faisal A. and Bogari, Neda M. and Taher, Mohiuddin M. and Athar, Mohammad and Schubert, Thomas and Habeebullah, Turki M. and Qari, Sameer H. (2021) Compound A Increases Cell Infiltration in Target Organs of Acute Graft-versus-Host Disease (aGVHD) in a Mouse Model. MOLECULES, 26 (14): 4237. ISSN , 1420-3049

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Abstract

Systemic steroids are used to treat acute graft-versus-host disease (aGVHD) caused by allogenic bone marrow transplantation (allo-BMT); however, their prolonged use results in complications. Hence, new agents for treating aGVHD are required. Recently, a new compound A (CpdA), with anti-inflammatory activity and reduced side effects compared to steroids, has been identified. Here, we aimed to determine whether CpdA can improve the outcome of aGVHD when administered after transplantation in a mouse model (C57BL/6 in B6D2F1). After conditioning with 9Gy total body irradiation, mice were infused with bone marrow (BM) cells and splenocytes from either syngeneic (B6D2F1) or allogeneic (C57BL/6) donors. The animals were subsequently treated (3 days/week) with 7.5 mg/kg CpdA from day +15 to day +28; the controls received 0.9% NaCl. Thereafter, the incidence and severity of aGVHD in aGVHD target organs were analyzed. Survival and clinical scores did not differ significantly; however, CpdA-treated animals showed high cell infiltration in the target organs. In bulk mixed lymphocyte reactions, CpdA treatment reduced the cell proliferation and expression of inflammatory cytokines and chemokines compared to controls, whereas levels of TNF, IL-23, chemokines, and chemokine receptors increased. CpdA significantly reduced proliferation in vitro but increased T cell infiltration in target organs.

Item Type: Article
Uncontrolled Keywords: GLUCOCORTICOID-RECEPTOR MODULATOR; BONE-MARROW-TRANSPLANTATION; IDIOPATHIC PNEUMONIA SYNDROME; T-CELLS; PLANT-ORIGIN; PREDNISONE; LIGAND; METHYLPREDNISOLONE; CORTICOSTEROIDS; INFLAMMATION; stem cell transplantation; graft-versus-host disease; compound A; bioactive compounds; T cells; cytokines; chemokine; bone marrow transplantation; mouse model
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 16 Sep 2022 06:47
Last Modified: 16 Sep 2022 06:47
URI: https://pred.uni-regensburg.de/id/eprint/47508

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