[Methylation status of the IL-10 gene promoter in the peripheral blood mononuclear cells of rheumatoid arthritis patients].
Interleukin 10(IL-10), as an immunoregulatory cytokine, plays an important role in rheumatoid arthritis (RA). IL-10 gene silencing is associated with the chromatin remodeling in differentiated Th1 and Th2 cells. To explore the relationship between IL-10 promoter methylation and gene silencing in the pathogenesis of RA, IL-10 mRNA, protein expression and promoter methylation status were analyzed in the peripheral blood mononuclear cells (PBMC) of 34 RA patients and 30 healthy controls by reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and methylation specific polymerase chain reaction (MSP), respectively. The results showed that IL-10 mRNA and protein expression in RA patients seemed to be lower than that in healthy controls, but there was no statistically significant difference (P>0.05). IL-10 promoter was methylated at a frequency of 85.29% in RA cases, which was significantly higher than the percentage in healthy controls (43.33%) (c 2 =12.439, P=0.000). IL-10 promoter methylation and mRNA expression showed a strong negative correlation (r=-0.579, P=0.001). IL-10 promoter methylation, but not mRNA expression, also correlated statistically with the number of arthritic joints. However, there were no statistical correlations between IL-10 promoter methylation (or mRNA expression) and clinical indices of RA, such as the levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and rheumatic factor (RF) or age (P>0.05). These findings suggest that promoter methylation may be a crucial mechanism of IL-10 gene inactivation in RA and IL-10 promoter CpG island hypermethylation might be involved in the occurrence and development of RA.
Fu
Li-Hong
LH
Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China. lihfu@126.com
Cong
Bin
B
Zhen
Yan-Feng
YF
Li
Shu-Jin
SJ
Ma
Chun-Ling
CL
Ni
Zhi-Yu
ZY
Zhang
Guo-Zhong
GZ
Zuo
Min
M
Yao
Yu-Xia
YX
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D012333:RNA, Messenger; D016753:Interleukin-10