PMID- 19651491 OWN - NLM STAT- MEDLINE DCOM- 20091102 LR - 20151119 IS - 1873-569X (Electronic) IS - 0923-1811 (Linking) VI - 56 IP - 1 DP - 2009 Oct TI - DNA demethylation of the perforin promoter in CD4(+) T cells from patients with subacute cutaneous lupus erythematosus. PG - 33-6 LID - 10.1016/j.jdermsci.2009.06.010 [doi] AB - BACKGROUND: Recent evidence indicates that human lupus is an epigenetic disease characterized by impaired T cell DNA methylation. Perforin, a cytotoxic effector molecule, is overexpressed due to hypomethylation of its promoter regulatory elements in CD4(+) T cells from patients with systemic erythematosus lupus (SLE). However, it is unknown whether aberrant expression and methylation of perforin occur in CD4(+) T cells from patients with subacute cutaneous lupus erythematosus (SCLE). OBJECTIVE: We aimed to compare the perforin expression level and the methylation status of the perforin promoter region in CD4(+) T cells from SCLE patients and healthy controls. METHODS: We used real-time RT-PCR to compare the perforin mRNA levels, and Western-blot to compare perforin protein levels in CD4(+) and CD8(+) T cells from SCLE patients and healthy controls. Bisulfite sequencing was used to determine the methylation status of the perforin promoter region. RESULTS: Perforin is overexpressed in SCLE CD4(+) T cells. Demethylation of the perforin promoter region was seen in CD4(+) T cells from patients with SCLE. CONCLUSIONS: DNA demethylation at the perforin locus contributes to perforin overexpression in SCLE CD4(+) T cells. FAU - Luo, Yongqi AU - Luo Y AD - Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, PR China. FAU - Zhang, Xiujuan AU - Zhang X FAU - Zhao, Ming AU - Zhao M FAU - Lu, Qianjin AU - Lu Q LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090803 PL - Netherlands TA - J Dermatol Sci JT - Journal of dermatological science JID - 9011485 RN - 0 (PRF1 protein, human) RN - 0 (Pore Forming Cytotoxic Proteins) RN - 0 (RNA, Messenger) RN - 126465-35-8 (Perforin) SB - IM MH - Adult MH - CD4-Positive T-Lymphocytes/*metabolism MH - CD8-Positive T-Lymphocytes/*metabolism MH - *DNA Methylation MH - Female MH - Humans MH - Lupus Erythematosus, Cutaneous/*genetics MH - Male MH - Middle Aged MH - Perforin MH - Pore Forming Cytotoxic Proteins/*genetics MH - Promoter Regions, Genetic/genetics/physiology MH - RNA, Messenger/metabolism EDAT- 2009/08/05 09:00 MHDA- 2009/11/03 06:00 CRDT- 2009/08/05 09:00 PHST- 2009/04/19 00:00 [received] PHST- 2009/06/23 00:00 [revised] PHST- 2009/06/28 00:00 [accepted] PHST- 2009/08/05 09:00 [entrez] PHST- 2009/08/05 09:00 [pubmed] PHST- 2009/11/03 06:00 [medline] AID - S0923-1811(09)00195-9 [pii] AID - 10.1016/j.jdermsci.2009.06.010 [doi] PST - ppublish SO - J Dermatol Sci. 2009 Oct;56(1):33-6. doi: 10.1016/j.jdermsci.2009.06.010. Epub 2009 Aug 3.