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.
Subject(s)
CD4-Positive T-Lymphocytes/drug effects , Inflammation/drug therapy , Lupus Erythematosus, Systemic/drug therapy , Stilbenes/administration & dosage , Animals , Antigens, CD/biosynthesis , Antigens, CD19/metabolism , Antigens, Differentiation, T-Lymphocyte/biosynthesis , Apoptosis/drug effects , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/immunology , Gene Expression Regulation/drug effects , Humans , Inflammation/chemically induced , Inflammation/immunology , Lectins, C-Type/biosynthesis , Lupus Erythematosus, Systemic/chemically induced , Lupus Erythematosus, Systemic/immunology , Mice , Receptors, Transferrin/biosynthesis , Resveratrol , Sirtuin 1/deficiency , Sirtuin 1/immunology , Terpenes/toxicityABSTRACT
OBJECTIVE: To study the effect of resveratrol on murine CD4(+);T lymphocyte activation. METHODS: Splenic mononuclear cells (SMCs) from specific pathogen free (SPF) BALB/c mice (female, aged 9-10 weeks) were cultured with resveratrol (0, 10, 20, and 40 mmol/L) for 30 min in vitro, and then were activated with ConA, anti-CD3 or anti-CD3/anti-CD28. At 6 h (for CD69) and 36 h (for CD71), cells were harvested for being stained with anti-CD4-PerCP and anti-CD69-FITC, or anti-CD4-PerCP and anti-CD71-FITC, and the expressions of CD69 and CD71 were detected respectively using flow cytometry. RESULTS: Resveratrol (≥10 mmol/L) significantly decreased CD69 levels on CD4(+);T lymphocytes activated with anti-CD3 in a dose-dependent manner (P<0.01). In addition, resveratrol (≥20 mmol/L) decreased CD69 levels on CD4(+);T lymphocytes activated with ConA, and anti-CD3/anti-CD28 in a dose-dependent manner (P<0.05). When concentrations ≥10 mmol/L, resveratrol depressed CD71 expression on ConA stimulated CD4(+);T lymphocytes (P<0.05), and resveratrol (≥20 mmol/L) decreased CD71 levels on anti-CD3 and anti-CD3/anti-CD28 stimulated CD4(+);T lymphocytes (P<0.05), all in a dose-dependent manner. CONCLUSION: Resveratrol inhibits the activation of murine CD4(+);T lymphocytes in a dosedependent manner.
Subject(s)
CD4-Positive T-Lymphocytes/drug effects , Immunosuppressive Agents/pharmacology , Lymphocyte Activation/drug effects , Stilbenes/pharmacology , Animals , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Immunophenotyping , Lectins, C-Type/metabolism , Lymphocyte Activation/immunology , Male , Mice , Receptors, Transferrin/metabolism , ResveratrolABSTRACT
OBJECTIVE: To determine the significance of hepatitis B virus (HBV)-associated antigen deposition in renal tissue from patients with systemic lupus erythematosus (SLE). METHODS: The medical records of 166 inpatients with lupus nephritis and 384 controls without SLE were analyzed retrospectively. Patients with SLE were classified as positive or negative depending on whether HBV-associated antigen deposition was detected in renal biopsies. RESULTS: HBV-associated antigen deposition was mainly detected in renal tissue from patients with SLE (50.6%), primary renal glomerular disease (20.8%), and allergic purpura (21.7%). It was not detected in renal tissue from patients with diabetic nephropathy, hypertensive nephrosclerosis, thin basement membrane nephropathy, or Alport syndrome. Hepatitis B surface antigen and core antigen were deposited in the mesangial region and vascular loops. The positive group had a significantly higher frequency of IgG, IgA, and IgM deposition than the negative group (53.6% vs 30.5%; p < 0.01). There was no significant difference in the types of lupus nephritis observed between the 2 groups. CONCLUSION: There was a high prevalence of HBV-associated antigen deposition in renal tissue of patients with SLE by indirect immunofluorescence, which may result mainly from the cross-reactivity with deposited immunoglobulins.
