Notch-1 Up-Regulation and Signaling following Macrophage Activation Modulates Gene Expression Patterns Known to Affect Antigen-Presenting Capacity and Cytotoxic Activity

摘要: Notch signaling has been extensively implicated in cell-fate determination along the development of immune system. However, a role for fully differentiated cells not clearly defined. We have analyzed expression protein family members during macrophage activation. Resting macrophages express Notch-1, -2, and -4, as well ligands Jagged-1 -2. After treatment with LPS and/or IFN-gamma, we observed p38 MAPK-dependent increase Notch-1 mRNA levels. To study activation, forced transient truncated, active intracellular (Notch-IC) proteins Raw 264.7 their effects on activity transcription factors involved Notch-IC increased STAT-1-dependent transcription. Furthermore, stable transfectants STAT1-dependent response to leading higher IFN regulatory factor-1, suppressor cytokine signaling-1, ICAM-1, MHC class II proteins. This effect was independent from an STAT1 Tyr or Ser phosphorylation. inducible NO synthase production decreased under same conditions. Our results show that up-regulation subsequent following activation modulate gene patterns known affect function mature macrophages.