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To investigate the role of Notch signaling pathway in immune thrombocytopenic purpura (ITP), we measured the expression of 11 Notch pathway molecules in ITP patients and evaluated their clinical relevance. Real-time reverse transcriptase polymerase chain reaction results showed there was aberrant expression of some Notch molecules in ITP. Notch1 and Notch3 expression elevated, while Notch2 decreased statistically in ITP patients. As for Notch ligands, only DLL1 was found downregulated in ITP. The expression of Notch target gene, Hes1, was also upregulated. In accordance with the mRNA level, Notch1 and Hes1 protein expression was also found elevated by Western blot. Immunocytochemistry showed that Notch1 expressed highly in the cytomembrane, cytoplasm, and part of cellular nucleus for ITP while weak in cytomembrane for controls, and Hes1 of ITP was found expressed higher in cellular nucleus than that of controls. Our findings suggest that the aberrant expression profile of Notch pathway may be involved in ITP, and blockage of Notch1 pathway is likely a promising therapeutic concept. [ABSTRACT FROM AUTHOR]

The data on polarization of the immune system towards T helper 1 (Th1) or T helper 2 (Th2) cells in immune thrombocytopenic purpura (ITP) are limited and contradictory. Th17 characterized by the production of Interleukin 17 (IL-17) has been shown to play a crucial part in the induction of autoimmune diseases. To further investigate the role of Th cytokines in the pathogenesis of ITP, we measured the plasma concentration of three Th17-associated cytokines [IL-17, transforming growth factor-ß (TGF-ß), IL-6] and Th1 cytokine interferon-γ (IFN-γ) in ITP patients, and evaluated their clinical relevance. The concentration of IL-17, TGF-ß, IL-6, and IFN-γ in plasma specimens from 29 adults with chronic ITP and 38 controls was analyzed by enzyme-linked immunosorbent assay method. No significant differences of Th17 cytokines (IL-17, TGF-ß, and IL-6) and Th1 cytokine (IFN-γ) concentration were observed between patients with active ITP and the control group. And the IFN-γ/IL-17 ratio representing Th1/Th17 cytokine profile was not significantly different between ITP patients and control, either. However, significantly positive correlation between IL-6 and IFN-γ in ITP patients was observed ( r = 0.48, P = 0.01). Among the ITP patients, Plasma IL-17 levels in male were marginally higher than those in female, while similar for TGF-ß, IL-6 or IFN-γ. There was a significantly positive correlation between age and IL-6 concentration in ITP patients ( r = 0.56, P = 0.0002), while no statistical significance between age and the other three cytokines. No significant correlation between cytokine concentrations and platelets or megakaryocytes number was found in ITP patients. In summary, ITP may not be associated with changes of plasma Th17 and Th1 cytokine concentrations relative to control population. [ABSTRACT FROM AUTHOR]