Abstract
FOXO forkhead transcription factors play an important role in controlling lymphocyte activation and proliferation. To evaluate the possibility that FOXO transcriptional expression is dysregulated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients, we determined the quantities of FOXO1, FOXO3a, and FOXO4 transcripts in peripheral blood mononuclear cells (PBMCs) from normal controls as well as from SLE and RA patients. Results showed that FOXO1 and FOXO3a are dominant FOXO factors at the transcript level in PBMCs. Statistical analysis showed that the FOXO1 transcript levels in RA patients and in SLE patients with active disease activity were significantly lower than those in normal controls, and the FOXO1 transcript levels were inversely correlated with lupus disease activity. In contrast, the differences in FOXO3a and FOXO4 transcript levels between normal controls and patients were not significant. These data suggest that the transcriptional dysregulation in FOXO1 is possibly linked to the pathogenesis of SLE and RA.
Highlights
The forkhead transcription factors, denoted as Forkhead-box (Fox) factors, belong to a group of nuclear proteins that contain conserved winged helix/ forkhead DNA binding domain [1]
Some representative reverse transcriptionpolymerase chain reaction (RT-PCR) results are shown in Figure 1, and it appears that all FOXO1, FOXO3a, and FOXO4 transcripts can be detected in peripheral blood mononuclear cells (PBMCs) of healthy individuals with slight interindividual variation
The transcript levels of FOXO genes in PBMCs were determined by quantifying the amounts of DNA products derived from the RT-PCR amplification of FOXO transcripts and were normalized according to GAPDH transcript levels, and FOXO1 and FOXO3a transcripts appeared to be more abundant than FOXO4 transcripts in normal PBMCs (Table 2)
Summary
The forkhead transcription factors, denoted as Forkhead-box (Fox) factors, belong to a group of nuclear proteins that contain conserved winged helix/ forkhead DNA binding domain [1]. The members of the forkhead box class O (FOXO) subfamily of forkhead transcription factors, FOXO1, FOXO3a, and FOXO4, have been shown to mediate various cellular functions, including cell proliferation, tumor suppression, metabolism, and oxidative stress responses [6,7]. The activities of these FOXO factors are tightly regulated at the protein level via posttranslational modification, including phosphorylation by kinases, such as protein kinase B
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