03 November 2017 : Original article
A New Concept of the Old Inhibitor NSC 74859 in Alleviating Cardiac Allograft Rejection and Extending Allograft Survival in Mice
Yiquan Lai1E, Feng Kuang1E, Zhonggui Shan1AB*, Huaqing Liu2EFDOI: 10.12659/AOT.905688
Ann Transplant 2017; 22:656-662
Abstract
BACKGROUND: STAT1/4 has been suggested to be involved in cardiac allograft rejection. However, no direct evidence regarding STAT3 has been established in cardiac allograft rejection. Here, we hypothesized that inhibition of STAT3 attenuates cardiac allograft rejection.
MATERIAL AND METHODS: To test our hypothesis, homotopic mouse heart transplantation was carried out in syngeneic C57BL/6 to C57BL/6 strain mice with or without oral gavage with NSC 74859, an inhibitor of STAT3. The immune response was investigated using real-time PCR for CD4 and CD8 surface makers of T cells and CD14 of monocytes and cytokines, including IL-2, IL-15, and IL-6 of allografts at 3, 6, and 9 days after transplantation. Prognosis was also evaluated.
RESULTS: We found that allografts with oral gavage of NSC 74859 whose CD4, CD8 T, and CD14 monocytes were significantly lower than that of allograft without oral gavage of NSC 74859, and the same was true for the expression of IL-2, IL-15, and IL-6. Immunohistochemical analysis of grafts showed reduced infiltration of monocytes/macrophages into the graft myocardium. Survival was also markedly extended in the NSC 74859 group.
CONCLUSIONS: Inhibition of IL-6/STAT3 using NSC 74859 was shown to remarkably alleviate cardiac allograft rejection in mice, indicating that the target against IL-6/STAT3 pathway might be clinically used as an alternative therapy for cardiac allograft rejection.
Keywords: Models, Animal, Receptors, Interleukin-6
In Press
18 Mar 2024 : Original article
Does Antibiotic Use Increase the Risk of Post-Transplantation Diabetes Mellitus? A Retrospective Study of R...Ann Transplant In Press; DOI: 10.12659/AOT.943282
20 Mar 2024 : Original article
Transplant Nephrectomy: A Comparative Study of Timing and Techniques in a Single InstitutionAnn Transplant In Press; DOI: 10.12659/AOT.942252
28 Mar 2024 : Original article
Association Between FEV₁ Decline Rate and Mortality in Long-Term Follow-Up of a 21-Patient Pilot Clinical T...Ann Transplant In Press; DOI: 10.12659/AOT.942823
02 Apr 2024 : Original article
Liver Transplantation from Brain-Dead Donors with Hepatitis B or C in South Korea: A 2014-2020 Korean Organ...Ann Transplant In Press; DOI: 10.12659/AOT.943588
Most Viewed Current Articles
05 Apr 2022 : Original article
Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver TransplantationDOI :10.12659/AOT.935604
Ann Transplant 2022; 27:e935604
12 Jan 2022 : Original article
Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...DOI :10.12659/AOT.934738
Ann Transplant 2022; 27:e934738
22 Nov 2022 : Original article
Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...DOI :10.12659/AOT.937988
Ann Transplant 2022; 27:e937988
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860