Functional characterization of human mannose-binding lectin-associated serine protease (MASP)-1/3 and MASP-2 promoters, and comparison with the C1s promoter.
The 5'-flanking regions of the genes encoding human mannose-binding lectin-associated serine protease (MASP)-1/3 and MASP-2, key enzymes in the lectin complement pathway, were isolated and characterized. The features of their promoters were compared with those of the human gene for C1s, the effector component of the classical pathway. The sequences upstream from the transcription start sites of the three genes contained the elements essential for transcription and liver-specific expression. Transient expression of constructs of these genes fused to the luciferase reporter gene confirmed their liver-specific expression and showed that the MASP promoters were slightly up-regulated by the presence of IL-1beta. The stimulatory effects of IL-1beta on MASP1/3 and MASP2 gene expression were abolished by the simultaneous presence of IL-6. MASP-1/3 promoter activity was also down-regulated by IFN-gamma. In contrast, C1s promoter activity was strongly up-regulated by IL-6, IL-1beta and IFN-gamma. These results indicate that IL-6 and IFN-gamma affect the expression of the MASP genes in a different fashion from that of the C1s gene, implying differential regulatory effects of these cytokines on the biosynthesis of lectin pathway-specific serine proteases and classical pathway-specific serine proteases.
D024506:5' Flanking Region / Q000235:genetics; D001483:Base Sequence; D003167:Complement Activation; D003173:Complement C1s / Q000235:genetics*; D017930:Genes, Reporter; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D050606:Mannose-Binding Protein-Associated Serine Proteases; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012697:Serine Endopeptidases / Q000235:genetics* / Q000502:physiology
D007375:Interleukin-1; D015850:Interleukin-6; D007371:Interferon-gamma; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases; D003173:Complement C1s