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.