The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of B...The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.展开更多
Objective To investigate the significance of interleukin-13 (IL-13) in patients with active lupus nephritis (LN).Methods Ten healthy volunteers and 16 patients with active LN were included in this study. The protein l...Objective To investigate the significance of interleukin-13 (IL-13) in patients with active lupus nephritis (LN).Methods Ten healthy volunteers and 16 patients with active LN were included in this study. The protein level of IL-13 in plasma was examined by enzyme linked immunosorbent assay (ELISA), and gene expression of IL-13 in peripheral blood mononuclear cells (PBMCs) by reverse transcription polymerase chain reaction (RT-PCR). Expression of IL-13 mRNA in renal tissue was studied by in situ hybridization (ISH) techniques.Results The level of IL-13 in plasma and the expression of IL-13 mRNA in PBMCs were significantly higher in LN patients than those in the controls ( P ＜ 0.001 ). Increased expression of IL-13 mRNA was detected in renal tissue of active LN patients compared to those in the controls ( P ＜ 0.001 ). Analysis of the linear correlation indicated that the level of IL-13 mRNA in the tubulointerstitial area in patients with active LN correlated with the concentration of serum creatinine (Scr), the glomerular activity index (GAl),the activity index of tubulointerstitium, and the level of serum C3 ( P ＜ 0.05 for each).Conclusion The elevation of IL-13 may play an important role inthe molecular pathogenesis of active LN.展开更多
文摘The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.
基金ThisstudywassupportedbytheFoundationofScientificResearchfromtheScienceCommitteeofGuangdong (No 1995 5 6 )
文摘Objective To investigate the significance of interleukin-13 (IL-13) in patients with active lupus nephritis (LN).Methods Ten healthy volunteers and 16 patients with active LN were included in this study. The protein level of IL-13 in plasma was examined by enzyme linked immunosorbent assay (ELISA), and gene expression of IL-13 in peripheral blood mononuclear cells (PBMCs) by reverse transcription polymerase chain reaction (RT-PCR). Expression of IL-13 mRNA in renal tissue was studied by in situ hybridization (ISH) techniques.Results The level of IL-13 in plasma and the expression of IL-13 mRNA in PBMCs were significantly higher in LN patients than those in the controls ( P ＜ 0.001 ). Increased expression of IL-13 mRNA was detected in renal tissue of active LN patients compared to those in the controls ( P ＜ 0.001 ). Analysis of the linear correlation indicated that the level of IL-13 mRNA in the tubulointerstitial area in patients with active LN correlated with the concentration of serum creatinine (Scr), the glomerular activity index (GAl),the activity index of tubulointerstitium, and the level of serum C3 ( P ＜ 0.05 for each).Conclusion The elevation of IL-13 may play an important role inthe molecular pathogenesis of active LN.
