5-Lipoxygenase Upregulation by Dexamethasone in Human Mast Cells
| Autor: | Alfredo Tursi, L. Macchia, Roberto Di Paola, Jesper Z. Haeggström, Filomena Macchia, Joseph H. Butterfield, Teresa Colamorea, Maria F. Caiaffa, Maria Carmela Guerrese |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Leukotrienes
5-Lipoxygenase-Activating Proteins Biophysics Biochemistry Dexamethasone Gene Expression Regulation Enzymologic Downregulation and upregulation medicine Humans Mast Cells RNA Messenger Northern blot Glucocorticoids Molecular Biology Glutathione Transferase Regulation of gene expression Arachidonate 5-Lipoxygenase biology Membrane Proteins Cell Biology Mast cell Molecular biology Enzyme assay Clone Cells Up-Regulation Blot medicine.anatomical_structure Arachidonate 5-lipoxygenase biology.protein Carrier Proteins medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 265:617-624 |
| ISSN: | 0006-291X |
| Popis: | In spite of intensive research, our understanding of the regulation of expression of 5-LO (the key enzyme in the leukotriene metabolism) remains fragmentary. We investigated the effects of dexamethasone on the expression of this gene in a binary model consisting of two clones of the human mast cell line HMC-1, one with a 5-LO-negative and the other with a 5-LO-positive phenotype, respectively. When dexamethasone was included in the culture medium at a physiologically relevant concentration, biosynthesis of 5-LO derivatives increased considerably not only in the 5-LO-negative HMC-1 cells (approx 10-fold) but also in the 5-LO-positive cells, characterized by an already substantial enzyme activity. Consistently, Northern blot analysis revealed that a dramatic increase in the abundance of 5-LO mRNA occurred when the cells were exposed to dexamethasone. Likewise, a significant increase in the immunoreactive 5-LO protein was detected by Western blotting. In contrast, dexamethasone seemed to have no effect on the expression of two other genes of pivotal importance in leukotriene biosynthesis, viz. FLAP and LTC(4) synthase. We conclude that in human mast cells glucocorticoids effectively and selectively upregulate the expression of 5-LO. |
| Databáze: | OpenAIRE |
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