TNF-α modulates expression of the circadian clock gene Per2 in rheumatoid synovial cells.
Scand J Rheumatol
; 42(4): 276-80, 2013.
Article
em En
| MEDLINE
| ID: mdl-23496259
ABSTRACT
OBJECTIVES:
To study the effect of tumour necrosis factor (TNF)-α, responsible for the inflammation and circadian rhythm of rheumatoid arthritis (RA), on the expression of circadian clock genes in primary cultured human rheumatoid synovial cells.METHOD:
The expression of circadian clock genes, including circadian locomotor output cycles kaput (Clock), brain and muscle Arnt-like protein-1 (Bmal1), period (Per)1/2, and cryptochrome (Cry)1/2, and the proline and acidic amino acid-rich basic leucine zipper (PAR bZip) genes, a transcriptional activator of Per2, including D site of albumin promoter binding protein (Dbp), hepatic leukaemia factor (Hlf), and thyrotroph embryonic factor (Tef), and a transcriptional repressor of Per2, E4-binding protein 4 (E4bp4), in TNF-α-stimulated synovial cells was determined by real-time polymerase chain reaction (PCR). The D-box motifs in the Per2 promoter were mutated by site-directed mutagenesis, and the promoter activity of the Per2 gene was examined using the luciferase assay.RESULTS:
TNF-α enhanced the mRNA expression of Bmal1 and Cry1 but did not affect that of Clock, Per1, or Cry2. However, TNF-α inhibited the mRNA expression of the Per2 gene, as well as Dbp, Hlf, and Tef, but enhanced the mRNA expression of E4bp4. Furthermore, TNF-α inhibited the transcriptional activity of the wild-type Per2 gene in a manner dependent on the D-box 1 and D-box 2 motifs in the Per2 promoter.CONCLUSIONS:
TNF-α modulates the expression of the Per2 gene through the D-box binding proteins DBP, HLF, TEF, and E4BP4, in rheumatoid synovial cells, and thereby may contribute to the pathogenesis of RA.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Mutagênese Sítio-Dirigida
/
Fator de Necrose Tumoral alfa
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Proteínas CLOCK
/
Relógios Circadianos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article