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Resveratrol possesses protective effects in a pristane-induced lupus mouse model.

Wang ZL, Luo XF, Li MT, Xu D, Zhou S, Chen HZ, Gao N, Chen Z, Zhang LL, Zeng XF - PLoS ONE (2014)

Bottom Line: To date, no therapy has been found to satisfactorily treat SLE.Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro.In vitro antibody production and proliferation of B cells were also inhibited.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

ABSTRACT

Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of autoantibodies. To date, no therapy has been found to satisfactorily treat SLE. SIRT1 deficiency results in the development of an autoimmune syndrome in mice, including a high titer of anti-nuclear antibody in serum, immunoglobulin deposition in the kidney, and immune complex glomerulonephritis. Resveratrol is an activator of SIRT1 and possesses anti-inflammation and immune-regulatory properties.

Objective: To evaluate the preventative effects of resveratrol on a pristane-induced lupus animal model and assess its putative immune modulation effects.

Methods: BALB/c mice received a single intraperitoneal injection of 0.5 ml of pristane on day 1 and then various doses of resveratrol were given to the mice daily starting on day 2 and continuing for seven months. The autoantibodies in serum and supernatants were measured. Single cells isolated from spleen, isolated CD4+ T cells, and CD19+ B cells were cultured with or without resveratrol in vitro and assessed by flow cytometry.

Results: Resveratrol attenuated proteinuria, immunoglobuin depositon in kidney, and glomerulonephritis as well as IgG1 and IgG2a in serum in pristane-induced lupus mice. Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro. In vitro antibody production and proliferation of B cells were also inhibited.

Conclusion: Resveratrol possesses protective effects in pristane-induced lupus mice and may represent a novel approach for the management of SLE.

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Effects of resveratrol on CD4+ T lymphocytes in vitro.Resveratrol suppresses CD69 (A, B, and C) and CD71 (D, E, and F) expression on CD4+ T cells in vitro (mean ± SD; A: n = 8; B: n = 6; C: n = 6; D: n = 8; E: n = 8; F: n = 7) Control: SMCs cultured with activator and without resveratrol. (G-H) Resveratrol suppresses cell proliferation. G: CD4+ T cells; H: SMCs. (mean ± SD; n = 6). (I) Resveratrol induces CD4+ T cell apoptosis (mean ± SD; n = 5) (★: P<0.05; ★★: P<0.01).
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pone-0114792-g005: Effects of resveratrol on CD4+ T lymphocytes in vitro.Resveratrol suppresses CD69 (A, B, and C) and CD71 (D, E, and F) expression on CD4+ T cells in vitro (mean ± SD; A: n = 8; B: n = 6; C: n = 6; D: n = 8; E: n = 8; F: n = 7) Control: SMCs cultured with activator and without resveratrol. (G-H) Resveratrol suppresses cell proliferation. G: CD4+ T cells; H: SMCs. (mean ± SD; n = 6). (I) Resveratrol induces CD4+ T cell apoptosis (mean ± SD; n = 5) (★: P<0.05; ★★: P<0.01).

Mentions: Freshly isolated SMCs from pristane-induced lupus mice were activated with ConA (2.5 µg/ml) with or without resveratrol and the levels of CD69 and CD71 were then measured, which are markers of CD4+ T lymphocyte activation. The expression level of CD69 on CD4+ T lymphocytes was 3.28±1.33% without activator, but when the cells were incubated with ConA and resveratrol (0, 10, 20, 40, or 80 µM), the levels increased to 81.88±6.98%, 75.04±14.19%, 72.60±9.28%, 62.98±12.02%, and 47.97±15.12%, respectively (Fig. 5A). Therefore, resveratrol signficantly decreased the level of CD69 expression on CD4+ T lymphocytes activated with ConA in a dose-dependent manner. Moreover, a similar effect of resveratrol on CD4+ T lymphocytes was observed when they were activated with anti-CD3 or anti-CD3/CD28 antibodies (Fig. 5B and C, respectively).


Resveratrol possesses protective effects in a pristane-induced lupus mouse model.

Wang ZL, Luo XF, Li MT, Xu D, Zhou S, Chen HZ, Gao N, Chen Z, Zhang LL, Zeng XF - PLoS ONE (2014)

Effects of resveratrol on CD4+ T lymphocytes in vitro.Resveratrol suppresses CD69 (A, B, and C) and CD71 (D, E, and F) expression on CD4+ T cells in vitro (mean ± SD; A: n = 8; B: n = 6; C: n = 6; D: n = 8; E: n = 8; F: n = 7) Control: SMCs cultured with activator and without resveratrol. (G-H) Resveratrol suppresses cell proliferation. G: CD4+ T cells; H: SMCs. (mean ± SD; n = 6). (I) Resveratrol induces CD4+ T cell apoptosis (mean ± SD; n = 5) (★: P<0.05; ★★: P<0.01).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4263676&req=5

pone-0114792-g005: Effects of resveratrol on CD4+ T lymphocytes in vitro.Resveratrol suppresses CD69 (A, B, and C) and CD71 (D, E, and F) expression on CD4+ T cells in vitro (mean ± SD; A: n = 8; B: n = 6; C: n = 6; D: n = 8; E: n = 8; F: n = 7) Control: SMCs cultured with activator and without resveratrol. (G-H) Resveratrol suppresses cell proliferation. G: CD4+ T cells; H: SMCs. (mean ± SD; n = 6). (I) Resveratrol induces CD4+ T cell apoptosis (mean ± SD; n = 5) (★: P<0.05; ★★: P<0.01).
Mentions: Freshly isolated SMCs from pristane-induced lupus mice were activated with ConA (2.5 µg/ml) with or without resveratrol and the levels of CD69 and CD71 were then measured, which are markers of CD4+ T lymphocyte activation. The expression level of CD69 on CD4+ T lymphocytes was 3.28±1.33% without activator, but when the cells were incubated with ConA and resveratrol (0, 10, 20, 40, or 80 µM), the levels increased to 81.88±6.98%, 75.04±14.19%, 72.60±9.28%, 62.98±12.02%, and 47.97±15.12%, respectively (Fig. 5A). Therefore, resveratrol signficantly decreased the level of CD69 expression on CD4+ T lymphocytes activated with ConA in a dose-dependent manner. Moreover, a similar effect of resveratrol on CD4+ T lymphocytes was observed when they were activated with anti-CD3 or anti-CD3/CD28 antibodies (Fig. 5B and C, respectively).

Bottom Line: To date, no therapy has been found to satisfactorily treat SLE.Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro.In vitro antibody production and proliferation of B cells were also inhibited.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

ABSTRACT

Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of autoantibodies. To date, no therapy has been found to satisfactorily treat SLE. SIRT1 deficiency results in the development of an autoimmune syndrome in mice, including a high titer of anti-nuclear antibody in serum, immunoglobulin deposition in the kidney, and immune complex glomerulonephritis. Resveratrol is an activator of SIRT1 and possesses anti-inflammation and immune-regulatory properties.

Objective: To evaluate the preventative effects of resveratrol on a pristane-induced lupus animal model and assess its putative immune modulation effects.

Methods: BALB/c mice received a single intraperitoneal injection of 0.5 ml of pristane on day 1 and then various doses of resveratrol were given to the mice daily starting on day 2 and continuing for seven months. The autoantibodies in serum and supernatants were measured. Single cells isolated from spleen, isolated CD4+ T cells, and CD19+ B cells were cultured with or without resveratrol in vitro and assessed by flow cytometry.

Results: Resveratrol attenuated proteinuria, immunoglobuin depositon in kidney, and glomerulonephritis as well as IgG1 and IgG2a in serum in pristane-induced lupus mice. Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro. In vitro antibody production and proliferation of B cells were also inhibited.

Conclusion: Resveratrol possesses protective effects in pristane-induced lupus mice and may represent a novel approach for the management of SLE.

Show MeSH
Related in: MedlinePlus