Dataset Information

Resveratrol attenuates stimulated T-cell activation and proliferation: potential therapy against cellular rejection in organ transplantation.

ABSTRACT:

Background

Pharmaceuticals to inhibit mammalian target of rapamycin (mTOR) protein, which plays an integral role in T cell survival and function, have been used to prevent complications associated with organ transplantation. Although studies have individually shown that resveratrol can inhibit mTOR and that inhibiting mTOR leads to attenuated immune function, no studies to date have examined these two functions conjointly under one study. Therefore, we hypothesize that resveratrol will decrease mTOR activation and expression as well as attenuate stimulated T cell activation and proliferation in peripheral blood mononuclear cells (PBMC).

Methods and materials

Human PBMC were isolated and cultured. The cells were pre-treated with resveratrol (50 ?M) overnight (18 hrs) before stimulation. The cells were collected for subsequent biochemical analysis after 1, 3, and 5 days. Additionally, the cells were stained with proliferation dye and cultured for 24 hours in PMA/Ionomycin with resveratrol for flow cytometry analysis.

Results

Resveratrol treated stimulated PBMCs displayed a significant decrease in activated phosphorylation of mTOR at days 1, 3, and 5 (P < 0.0329). Markers of T cell activation, tumour necrosis factor-alpha (TNF-?) and interferon-gamma (INF-?), were also significantly reduced along with T cell proliferation following stimulated PBMC resveratrol treatment when compared to vehicle-treated controls (P < 0.01).

Conclusion

Taken together, our data suggest that resveratrol can decrease the immune response of stimulated T-cells and inhibit the expression and activation of mTOR mediated cellular signalling under the same study setting. Therefore, resveratrol proposes a possible adjunctive therapy option for patients undergoing organ transplantation.

SUBMITTER: Kang JJ

PROVIDER: S-EPMC7811925 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Resveratrol attenuates stimulated T-cell activation and proliferation: potential therapy against cellular rejection in organ transplantation.

Kang Jimmy Jh JJ Bozso Sabin J SJ Boe Dana E DE Al-Adra David P DP Moon Michael C MC Freed Darren H DH Nagendran Jayan J Nagendran Jeevan J

American journal of clinical and experimental immunology 20201215 5

<h4>Background</h4>Pharmaceuticals to inhibit mammalian target of rapamycin (mTOR) protein, which plays an integral role in T cell survival and function, have been used to prevent complications associated with organ transplantation. Although studies have individually shown that resveratrol can inhibit mTOR and that inhibiting mTOR leads to attenuated immune function, no studies to date have examined these two functions conjointly under one study. Therefore, we hypothesize that resveratrol will d ...[more]

PMID: 33489476

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Project description:BackgroundCostimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.Materials and methodsThe rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.ResultsIn rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.ConclusionBelatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.

Dataset Information

Resveratrol attenuates stimulated T-cell activation and proliferation: potential therapy against cellular rejection in organ transplantation.

Background

Methods and materials

Results

Conclusion

Publications

Resveratrol attenuates stimulated T-cell activation and proliferation: potential therapy against cellular rejection in organ transplantation.

Similar Datasets

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