Regulation Of Leukotriene C4 Synthase Gene Expression By Sp1 And Sp3 In Mononuclear Phagocytes
A large body of experimental evidence has implicated the cysteinyl leukotrienes in a variety of inflammatory responses201C;2. Leukotriene C4 (LTC4) synthase (Mr of 16,568; EC#22.214.171.124) is a selective, membrane-bound glutathione-S-transferase that catalyzes the conversion of LTA4 to LTC4. Although LTC4 synthase enzymatic activity is found in various cell types, mRNA for LTC4 synthase is present only in eosinophils, basophils, mast cells, and cells of monocyte/macrophage lineage. Previous studies suggest that LTC4 synthase expression is increased in the bronchial mucosa of patients with aspirin-sensitive asthma3. The gene for LTC4 synthase has been cloned, sequenced, and mapped to the distal region of chromosome 54’5. The LTC4 synthase 5’ flanking region lacks a TATA box but has known consensus sites for ets, AP-1, AP-2, and Sp14’5. Previous work from our laboratory indicates that LTC4 synthase gene expression is upregulated by transforming growth factor-ß (TGF-ß) through a transcriptional mechanism in the monocyte-like cell line, THP-16. The purpose of this study was to begin to investigate the molecular mechanisms of regulation of transcription of the LTC4 synthase gene in mononuclear phagocytes.
KeywordsHeLa Cell Electrophoretic Mobility Shift Assay Reporter Activity Consensus Site HeLa Nuclear Extract
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