Combined nifuroxazide and SAT05f therapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation.

Abstract

Acute graft-versus-host disease (aGvHD) is the major barrier to the broader use of allogenetic hematopoietic stem cells. However, currently these are no highly specific and efficient drugs. Monotherapy is not sufficient and more efficient and safe therapeutic regimen are urgent need. Studies demonstrated TLR9 and Stat3 signal pathways are critical for antigen-presenting cell maturation and T-cell activation, which are important mediators in aGvHD. Specific block these two critical signal pathways using their inhibitors SAT05f and nifuroxazide may be the novel strategies for aGvHD therapy. The results showed combined therapy significantly decreased the severity of aGvHD and prolonged the survival rate. Furthermore, after treatment, the activation of CD4+ effect T cells was reduced, whereas Treg cells was increased, and the cytokine release was inhibited. In conclusion, combined therapy of nifuroxazide with SAT05f may be potential for the prevention or treatment of aGvHD, providing theoretic and experimental basis.

• Authors: Huijie Jia, Tiesuo Zhao, Yinghua Ji, Xiaolong Jia, Wenjing Ren, Chen Li, Minming Li, Yali Xiao, Hui Wang, Kailin Xu
• Journal: Cell death & disease (Cell Death Dis) Vol. 7 Issue 12 Pg. e2507 (12 01 2016) ISSN: 2041-4889 [Electronic] England
• PMID: 27906171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Hydroxybenzoates
• Nitrofurans
• Oligodeoxyribonucleotides
• SAT05f
• STAT3 Transcription Factor
• Toll-Like Receptor 9
• nifuroxazide

Topics

• Animals
• Bone Marrow Transplantation (adverse effects)
• Cell Differentiation (drug effects)
• Cytokines (blood)
• Drug Therapy, Combination
• Graft vs Host Disease (blood, drug therapy, etiology)
• Hydroxybenzoates (administration & dosage, therapeutic use)
• Lymphocyte Activation (drug effects)
• Lymphocyte Count
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Models, Biological
• Nitrofurans (administration & dosage, therapeutic use)
• Oligodeoxyribonucleotides (administration & dosage, therapeutic use)
• Organ Specificity
• STAT3 Transcription Factor (metabolism)
• Severity of Illness Index
• Survival Analysis
• T-Lymphocytes, Regulatory (drug effects)
• Toll-Like Receptor 9 (metabolism)
• Transplantation, Homologous