BACKGROUND: An imbalance of Th1 and Th2 cytokines has been reported in MCNS. Interleukin-13 (IL-13: Th2 cytokine) has been implicated in the pathogenesis of MCNS, but Th1/Th2 regulators such as T-bet (Th1-specific transcription factor) and GATA-3 (Th2-specific transcription factor) have not been examined. METHODS: We isolated PBMC from 25 patients with MCNS during nephrosis and remission phases, from 17 nephrotic patients with membranous nephropathy (MN), and from 25 healthy subjects. We measured mRNA expression levels of T-bet, GATA-3, Stat5A (regulator of Th2 priming), IFN-gamma (Th1 cytokine), IL-2 (Th1 cytokine and activator of Stat5), IL-4 (Th2 cytokine), and IL-13 in PBMC, using real-time RT-PCR. RESULTS: GATA-3, Stat5A, and IL-13 mRNA expression levels were higher in the nephrotic MCNS group compared to the others. IL-2 mRNA expression levels were higher in nephrotic patients with MCNS and MN than in MCNS patients in remission and healthy controls. There were no differences in mRNA expression levels of T-bet, IFN-gamma, and IL-4 between MCNS and MN patients and healthy controls. CONCLUSIONS: This study is the first to reveal increased mRNA expression levels of GATA-3 and Stat5A in PBMC from MCNS patients in nephrosis. This study also supports recent findings suggesting the role of IL-13 in the development of MCNS. A predominant Th2 type of T cell activation may be involved in the pathogenesis of MCNS.
BACKGROUND: An imbalance of Th1 and Th2 cytokines has been reported in MCNS. Interleukin-13 (IL-13: Th2 cytokine) has been implicated in the pathogenesis of MCNS, but Th1/Th2 regulators such as T-bet (Th1-specific transcription factor) and GATA-3 (Th2-specific transcription factor) have not been examined. METHODS: We isolated PBMC from 25 patients with MCNS during nephrosis and remission phases, from 17 nephroticpatients with membranous nephropathy (MN), and from 25 healthy subjects. We measured mRNA expression levels of T-bet, GATA-3, Stat5A (regulator of Th2 priming), IFN-gamma (Th1 cytokine), IL-2 (Th1 cytokine and activator of Stat5), IL-4 (Th2 cytokine), and IL-13 in PBMC, using real-time RT-PCR. RESULTS:GATA-3, Stat5A, and IL-13 mRNA expression levels were higher in the nephroticMCNS group compared to the others. IL-2 mRNA expression levels were higher in nephroticpatients with MCNS and MN than in MCNSpatients in remission and healthy controls. There were no differences in mRNA expression levels of T-bet, IFN-gamma, and IL-4 between MCNS and MN patients and healthy controls. CONCLUSIONS: This study is the first to reveal increased mRNA expression levels of GATA-3 and Stat5A in PBMC from MCNSpatients in nephrosis. This study also supports recent findings suggesting the role of IL-13 in the development of MCNS. A predominant Th2 type of T cell activation may be involved in the pathogenesis of MCNS.
Authors: Daniel H Libraty; Satu Mäkelä; Jennifer Vlk; Mikko Hurme; Antti Vaheri; Francis A Ennis; Jukka Mustonen Journal: PLoS One Date: 2012-04-16 Impact factor: 3.240