BACKGROUND: CD4+ T cells DNA hypomethylation is involved in the pathogenesis of systemic lupus erythematosus (SLE). Recent studies showed that ultraviolet B (UVB, 290-320 nm) might induce the exacerbation of SLE by decreasing the DNA methylation level. However, the role of DNA methyltransferase 1 (DNMT1) in the UVB-induced CD4+ T cells DNA hypomethylation remains unclear. OBJECTIVE: To elucidate the role of DNMT1 in lupus CD4+ T cells global DNA hypomethylation enhanced by UVB. METHODS: 35 SLE patients and 15 healthy controls were enrolled in the study. CD4+ T cells from SLE patients and healthy controls exposed to different dosages of UVB were analyzed. The global DNA methylation measurement, real-time PCR, Western blotting and DNMT1 catalytic activity detection were employed. RESULTS: The level of global DNA methylation and DNMT1 mRNA expression in CD4+ T cells from SLE patients were significantly lower than those from the control group. DNA methylation was decreased after UVB exposure in a dosage-dependent manner in SLE patients, but not in the control group. DNMT1 mRNA and protein expression level were not affected by UVB exposure in both SLE patients and healthy controls. DNMT1 catalytic activity was significantly decreased in CD4+ T cells from SLE patients after UVB exposure in a dosage-dependent manner. DNMT1 catalytic activity was lower and more sensitive to UVB exposure in CD4+ T cells from active SLE patients that from stable ones. CONCLUSION: UVB enhanced DNA hypomethylation of CD4+ T cells in SLE via inhibiting DNMT1 catalytic activity in a dosage-dependent manner.
BACKGROUND:CD4+ T cells DNA hypomethylation is involved in the pathogenesis of systemic lupus erythematosus (SLE). Recent studies showed that ultraviolet B (UVB, 290-320 nm) might induce the exacerbation of SLE by decreasing the DNA methylation level. However, the role of DNA methyltransferase 1 (DNMT1) in the UVB-induced CD4+ T cells DNA hypomethylation remains unclear. OBJECTIVE: To elucidate the role of DNMT1 in lupus CD4+ T cells global DNA hypomethylation enhanced by UVB. METHODS: 35 SLEpatients and 15 healthy controls were enrolled in the study. CD4+ T cells from SLEpatients and healthy controls exposed to different dosages of UVB were analyzed. The global DNA methylation measurement, real-time PCR, Western blotting and DNMT1 catalytic activity detection were employed. RESULTS: The level of global DNA methylation and DNMT1 mRNA expression in CD4+ T cells from SLEpatients were significantly lower than those from the control group. DNA methylation was decreased after UVB exposure in a dosage-dependent manner in SLEpatients, but not in the control group. DNMT1 mRNA and protein expression level were not affected by UVB exposure in both SLEpatients and healthy controls. DNMT1 catalytic activity was significantly decreased in CD4+ T cells from SLEpatients after UVB exposure in a dosage-dependent manner. DNMT1 catalytic activity was lower and more sensitive to UVB exposure in CD4+ T cells from active SLEpatients that from stable ones. CONCLUSION: UVB enhanced DNA hypomethylation of CD4+ T cells in SLE via inhibiting DNMT1 catalytic activity in a dosage-dependent manner.
Authors: Min Zhang; Xuan Fang; Guo-Sheng Wang; Yan Ma; Li Jin; Xiao-Mei Li; Xiang-Pei Li Journal: Inflammopharmacology Date: 2017-02-11 Impact factor: 4.473
Authors: Stella Aslibekyan; Hassan S Dashti; Toshiko Tanaka; Jin Sha; Luigi Ferrucci; Degui Zhi; Stefania Bandinelli; Ingrid B Borecki; Devin M Absher; Donna K Arnett; Jose M Ordovas Journal: Chronobiol Int Date: 2014-07-30 Impact factor: 2.877