Therapeutic effects of STAT3 inhibition by nifuroxazide on murine acute graft graft-vs.-host disease: Old drug, new use.

Abstract

Graft‑vs.‑host disease (GvHD) is a major and lethal complication of allogeneic bone marrow transplantation (allo‑BMT). Although great development has been made, the treatment progress of this disorder is slow. Research has illustrated that STAT3 was critical for T cell alloactivation in GvHD. In the present study, the authors hypothesized that nifuroxazide, as the STAT3 inhibitor, treatment may attenuate the development of acute GvHD (aGvHD). The results demonstrated that nifuroxazide suppressed the development of aGvHD and significantly delayed aGvHD‑induced lethality. Mice receiving nifuroxazide had mostly normal‑appearing skin with minimal focal ulceration, mild edema and congestion in the liver, and a less‑pronounced villus injury and less inflammatory infiltrate in the small intestine. Treatment with nifuroxazide inhibited the activation of STAT3, resulting in the regulation of the CD4+ T cells and CD4+CD25+ T cells and reduction of interferon‑γ and tumor necrosis factor‑α levels. In conclusion, nifuroxazide may be efficacious for post‑transplant of GvHD, providing a potent drug for use as a prophylactic or as a second‑line therapy for aGvHD in clinical trials.

• Authors: Huijie Jia, Jing Cui, Xiaolong Jia, Jingjing Zhao, Yuchen Feng, Peijuan Zhao, Dan Zang, Jian Yu, Tiesuo Zhao, Hui Wang, Kailin Xu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 16 Issue 6 Pg. 9480-9486 (Dec 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 29152660 (Publication Type: Journal Article)

Chemical References

• Hydroxybenzoates
• Nitrofurans
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• nifuroxazide

Topics

• Animals
• Bone Marrow Transplantation (adverse effects)
• CD4-Positive T-Lymphocytes (drug effects)
• Gene Expression Regulation (drug effects)
• Graft vs Host Disease (drug therapy, etiology, genetics, pathology)
• Humans
• Hydroxybenzoates (administration & dosage)
• Interferon-gamma (genetics)
• Lymphocyte Activation (drug effects)
• Mice
• Nitrofurans (administration & dosage)
• STAT3 Transcription Factor (antagonists & inhibitors, genetics)
• Transplantation, Homologous (adverse effects)
• Tumor Necrosis Factor-alpha (genetics)