Alantolactone ameliorates graft versus host disease in mice
 
Yazarlar (17)
Gül Pelin Odabaş
Türkiye
Pınar Alisan Suna
Perihan Kader Kendirli
Makale Türü Açık Erişim Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
Dergi Adı International Immunopharmacology (Q1)
Dergi ISSN 1567-5769 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce Basım Tarihi 02-2024
Cilt / Sayı / Sayfa 128 / 0 / – DOI 10.1016/j.intimp.2024.111560
Makale Linki http://dx.doi.org/10.1016/j.intimp.2024.111560
Özet
The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8 T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L CD44). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in pro-inflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.
Anahtar Kelimeler
Alantolactone | Graft versus host disease | Bone marrow transplantation | Allogenic transplantation | Autoimmunity
BM Sürdürülebilir Kalkınma Amaçları
Atıf Sayıları
Web of Science 3
Alantolactone ameliorates graft versus host disease in mice

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