Abstract
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.
Keywords
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References
- The genetics and epigenetics of autoimmune diseases.J Autoimmun. 2009; 33: 3-11
- CD4+ cells treated with DNA methylation inhibitors induce autologous B cell differentiation.Clin Immunol Immunopathol. 1990; 55: 368-381
- Epigenetics: regulation through repression.Science. 1999; 286: 481-486
- DNA methylation in systemic lupus erythematosus.Lupus. 2003; 12: 79-85
- Mechanisms of epigenetic inheritance.Curr Opin Cell Biol. 2007; 19: 266-272
- Inhibition of DNA methyltransferase activity and expression by treatment with the pan-deacetylase inhibitor panobinostat in hepatocellular carcinoma cell lines.BMC Cancer. 2012; 12: 386-392
- Procainamide inhibits DNA methyltransferase in a human T cell line.J Rheumatol. 1991; 18: 530-534
- Drug-induced lupus: an update.Autoimmun Rev. 2010; 10: 46-50
- Prevalence and expression of photosensitivity in systemic lupus erythematosus.Ann Rheum Dis. 1989; 48: 461-463
- Methylation of deoxycytidine incorporated by excision-repair synthesis of DNA.Cell. 1982; 30: 509-516
- Ultraviolet radiation induced metallothionein-I gene activation is associated with extensive DNA demethylation.Cell. 1983; 35: 207-214
- A comparison of the specificity of the 1971 and 1982 American Rheumatism Association criteria for the classification of systemic lupus erythematosus.Arthritis Rheum. 1985; 28: 620-623
- Global solar UV index: a practical guide.World Health Organization, Geneva, Switzerland2002
- Australia has more than enough solar UV radiation.Clin Exp Optom. 2003; 86: 71-73
- DNA global hypomethylation in EBV-transformed interphase nuclei.Exp Cell Res. 1999; 249: 46-53
- Epigenomic stress response.J Biol Chem. 2003; 278: 14985-14995
- Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus.Arthritis Rheum. 2002; 46: 1282-1291
- Demethylation of the same promoter sequence increases CD70 expression in lupus T cells and T cells treated with lupus-inducing drugs.J Immunol. 2005; 174: 6212-6219
- In vitro ultraviolet irradiation induces proinflammatory responses in cells from premorbid SLE mice.Lupus. 2001; 10: 272-283
- Type I interferons are involved in the development of UVB-induced inflammatory skin lesions in Systemic Lupus Erythematosus (SLE) patients.Ann Rheum Dis. 2008; 67: 11-18
- Maintenance DNA methyltransferase (Met1) and silencing of CpG-methylated foreign DNA in Volvox carteri.Plant Mol Biol. 2007; 63: 325-336
- Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling.Arthritis Rheum. 2003; 48: 746-756
- Analysis of associations between the patterns of global DNA hypomethylation and expression of DNA methyltransferase in patients with systemic lupus erythematosus.Int J Dermatol. 2011; 50: 697-704
- Associations between aberrant DNA methylation and transcript levels of DNMT1 and MBD2 in CD4+T cells from patients with systemic lupus erythematosus.Australas J Dermatol. 2012; https://doi.org/10.1111/j.1440-0960.2012.00968.x
- Associations between the expression of epigenetically regulated genes and the expression of DNMTs and MBDs in systemic lupus erythematosus.PLoS ONE. 2012; 7: e45897https://doi.org/10.1371/journal.pone.0045897
- Ultraviolet B exposure of peripheral blood mononuclear cells of patients with systemic lupus erythematosus inhibits DNA methylation.Lupus. 2009; 18: 1037-1044
- DNA methylation in cancer: too much, but also too little.Oncogene. 2002; 21: 5400-5413
- Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration.Dev Biol. 2009; 334: 213-223
- DNMT1 modulates gene expression without its catalytic activity partially through its interactions with histone-modifying enzymes.Nucleic Acids Res. 2012; 40: 4334-4346
Article info
Publication history
Published online: May 24, 2013
Accepted:
April 18,
2013
Received in revised form:
April 11,
2013
Received:
February 28,
2013
Identification
Copyright
© 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
