TY - JOUR
T1 - 5-Lipoxygenase upregulation by dexamethasone in human mast cells
AU - Colamorea, Teresa
AU - Di Paola, Roberto
AU - Macchia, Filomena
AU - Guerrese, Maria Carmela
AU - Tursi, Alfredo
AU - Butterfield, Joseph H.
AU - Caiaffa, Maria F.
AU - Haeggström, Jesper Z.
AU - Macchia, Luigi
N1 - Funding Information:
The authors thank Francesca Fornelli, Ph.D., for valuable contribution to the cell cloning work, and Mattias Sjöström, M.Sc., for providing human LTC4 synthase cDNA. This work was supported by the European Union, Contract BMH4-CT96-0229; the Italian Association for Research on Cancer (AIRC), Milan; the Italian National Council of Research (CNR), Rome, Grant AI 98.00161.04; the Italian Ministry for University and Scientific and Technologic Research (MURST), Rome, COFIN97; and the Swedish Medical Research Council (10350).
PY - 1999/11/30
Y1 - 1999/11/30
N2 - 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 LTC4 synthase. We conclude that in human mast cells glucocorticoids effectively and selectively upregulate the expression of 5-LO.
AB - 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 LTC4 synthase. We conclude that in human mast cells glucocorticoids effectively and selectively upregulate the expression of 5-LO.
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U2 - 10.1006/bbrc.1999.1732
DO - 10.1006/bbrc.1999.1732
M3 - Article
C2 - 10600470
AN - SCOPUS:0033619779
SN - 0006-291X
VL - 265
SP - 617
EP - 624
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -