ABSTRACT
BACKGROUND: Aplastic anemia (AA) is an autoimmune disease and interleukin-27 (IL-27) is an important cytokine involved in the pathogenesis of autoimmune diseases. To date there have been no reports concerning the intrinsic association among IL-27 and Thelper (Th) 1 and Th17 cells in AA. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) to assay IL-27, interferon gamma (IFN-γ) and IL-17 levels, flow cytometry to measure the percentages of Th1 and Th17 cells among peripheral blood mononuclear cells (PBMCs), real-time reverse transcriptase polymerase chain reaction (PCR) for the mRNA levels of IL-27, IFN-γ, T-bet and IL-17 and retinoid related orphan receptor gamma (RORγt) in PBMCs were performed. In addition, the effect of exogenous rhIL-27 on the differentiation of T cells into Th1 and Th17 cells was investigated in vitro. RESULTS: Plasma and mRNA levels of IL-27 in PBMCs from AA patients were significantly higher than those in healthy controls. A positive correlation was found between plasma levels of IL27 and IFN-γ. The proportions of Th1 and Th17 cells accompanied by the mRNA expression of RORγt and T-bet were significantly higher in AA patients than in healthy controls. Plasma levels of IL-27 correlated positively with frequencies of Th1 cells in AA patients. Exogenous rhIL-27 could significantly upregulate the frequency of Th1 cells and the mRNA levels of T-bet and IFN-γ and the application of rhIL-27 in vitro could inhibit the expression of RORγt mRNA. CONCLUSION: The upregulation of IL-27 might cause Th1 differentiation and immune disorders in AA patients. Blocking the expression of IL-27 could therefore be a reasonable therapeutic strategy for AA.
Subject(s)
Anemia, Aplastic/immunology , Anemia, Aplastic/metabolism , Interleukin-17/metabolism , Th1 Cells/immunology , Th17 Cells/immunology , Adolescent , Adult , Aged , Anemia, Aplastic/genetics , Female , Gene Expression Regulation/drug effects , Humans , Interferon-gamma/blood , Interferon-gamma/genetics , Interleukin-17/blood , Interleukin-17/genetics , Interleukin-17/pharmacology , Male , Middle Aged , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , RNA, Messenger/genetics , T-Box Domain Proteins/genetics , Th1 Cells/drug effects , Th17 Cells/drug effects , Young AdultABSTRACT
Protein tyrosine phosphatase SHP2 plays a crucial role in the development of the central nervous system. To explore the expression and possible role of SHP2 during the course of bacterial meningitis, this article reports a juvenile rat bacterial meningitis model established by direct intracisternal injection of Streptococcus pneumoniae. Expression of SHP2 at both mRNA and protein levels were assessed. White blood cell count and concentration of tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) were also measured. In the cortex, bacterial meningitis led to a significant upregulation of mRNA encoding SHP2. SHP2 protein levels and CSF white blood cell count were positively correlated. However, there was no significant correlation between the levels of SHP2 protein and TNF-alpha concentrations in CSF. These findings do not support an essential role of SHP2 in the pathogenesis of experimental pneumoniae meningitis, but it is possible that SHP2 protein expression may be used as a marker of disease activity.
