Objective: FoxO3a is a transcriptional factor implicated in cell cycle regulation and apoptosis. Since rheumatoid arthritis (RA) is associated with apoptosis defects, we investigated FoxO3a expression level, regulation and phosphorylation status in RA blood and synovium.
Methods: In microarray experiments, an overexpression of FoxO3a mRNA was observed in RA blood compared to healthy controls. FoxO3a mRNA expression was quantified in RA polymorphonuclear (PMN) and peripheral blood mononuclear cells (PBMC) by qRT-PCR. Total FoxO3a and phosphorylated FoxO3a (pFoxO3a) protein expression was analyzed in blood leukocytes from RA vs. controls and in RA vs. OA synovium by immunostaining.
Results: FoxO3a mRNA and protein expression levels were increased in RA blood compared to controls. FoxO3a overexpression was primarily observed in PMNs. In RA synovium, both total and inactive phosphorylated FoxO3a proteins were detected. FoxO3a was detected primarily in the sublining T lymphocytes of RA synovium compared to the lining layer in RA and OA tissue, underlying a role for FoxO3a proteins in RA inflammation.
Conclusion: The overexpression of FoxO3a in RA blood, particularly in PMNs, suggests a potential role for this gene in RA pathogenesis through increased survival of blood PMNs. In RA synovium, FoxO3a mainly detected in inflammatory aggregates may also regulate the chronic survival of T lymphocytes.