Enhanced activation of Notch signaling in peripheral blood T helper cells of patients with rheumatoid arthritis (99.21)

Abstract

Abstract Expression of Notch homologues in local inflammation issue of rheumatoid arthritis (RA) and cultured synoviocytes has been reported, but the expression profile of Notch-related molecules in peripheral lymphocyte in RA remains unclear. Here, the expression of Notch receptors in peripheral lymphocytes of RA patients was assessed by both flow cytometry and real-time polymerase chain reaction (PCR). The expression of Notch target gene HES-1, regulatory gene NUMB and Notch-ICD was determined by PCR and immunoblot. There was an increased expression of Notch 2, Notch 3 and Notch 4 in T helper cells from active RA patients among which increased Notch 3 was mainly expressed by activated T cells. Notably, Notch 3-expressing T cells decreased in inactive RA patients and the level was similar to that of healthy controls (HC). T helper cells from RA patients exhibited increased expression of target gene HES-1 but decreased expression of negative modulation gene NUMB of Notch signaling. There was also an increased nuclear translocation of Notch-ICD in active RA disease. The present study demonstrate that T helper cells from RA patients display significantly altered expression profile of Notch receptors and enhanced activation of Notch signaling compared with those from HC. This study was supported by grants from the Natural Science Foundation of China (30872335) and Society Development Foundation of Zhenjiang (SH2008035).