Glucocorticoids up-regulate leukotriene B4 receptor-1 expression during neutrophilic differentiation of HL-60 cells.
Leukotriene B(4) (LTB(4)) is a potent activator of granulocytes and macrophages. The actions of LTB(4) are mediated by the specific G protein-coupled receptors, BLT1 and BLT2. We report up-regulation of BLT1 expression by dexamethasone (Dex), a synthetic glucocorticoid, in a promyelocytic cell line HL-60 during differentiation by retinoic acid (RA) into neutrophilic phenotype. The expression of BLT1 mRNA was also augmented by Dex in DMSO-differentiated neutrophilic HL-60 cells, but not in vitamin D(3)-differentiated monocytic HL-60 cells. Augmented expression of BLT1 by Dex was associated with enhanced functional activities, such as LTB(4)-induced intracellular calcium mobilization and chemotaxis. On the other hand, Dex failed to enhance BLT2 expression in RA-differentiated HL-60 cells, indicating different transcriptional regulations for these two receptors in spite of the fact that their genes are closely located (J. Exp. Med. 192 (2000) 413-420). These results suggest glucocorticoids enhance the functions of neutrophils during differentiation by up-regulating BLT1 expression, thus contributing to host defense.
Obinata
Hideru
H
Department of Biochemistry, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, Japan.
Yokomizo
Takehiko
T
Shimizu
Takao
T
Izumi
Takashi
T
D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002633:Chemotaxis; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000096:biosynthesis*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation
D005938:Glucocorticoids; C000607071:RARA protein, human; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018102:Receptors, Leukotriene B4; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; C411470:glucocorticoid receptor alpha; D014212:Tretinoin; D003907:Dexamethasone; D002118:Calcium