Glucocorticoids up-regulate leukotriene B4 receptor-1 expression during neutrophilic differentiation of HL-60 cells

Biochem Biophys Res Commun. 2003 Sep 12;309(1):114-9. doi: 10.1016/s0006-291x(03)01554-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcium / metabolism
  • Cell Differentiation
  • Chemotaxis
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Glucocorticoids / metabolism*
  • HL-60 Cells
  • Humans
  • Neutrophils / cytology*
  • Neutrophils / metabolism
  • Phenotype
  • Protein Binding
  • RNA, Messenger / metabolism
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Leukotriene B4 / biosynthesis*
  • Receptors, Retinoic Acid / metabolism
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tretinoin / pharmacology
  • Up-Regulation*

Substances

  • Glucocorticoids
  • RARA protein, human
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Receptors, Leukotriene B4
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Transcription Factors
  • glucocorticoid receptor alpha
  • Tretinoin
  • Dexamethasone
  • Calcium