Disodium cromoglycate suppresses the induction of cysteinyl leukotriene synthesis during granulocytic differentiation in HL-60 cells

Respir Med. 2004 Mar;98(3):235-41. doi: 10.1016/j.rmed.2003.09.016.

Abstract

Objectives: Disodium cromoglycate (DSCG) and nedocromil sodium are anti-asthma drugs that have a variety of physiological and biological effects. We examined whether DSCG affects the induction of cysteinyl Leukotriene (cysLT) synthesis during dimethyl sulfoxide (DMSO)-induced granulocytic differentiation in HL-60 cells.

Methods: HL-60 cells were differentiated to mature granulocyte-like cells by DMSO in the presence or absence of DSCG for 5 days. Then, we measured A23187-stimulated production of LTC4, an initial product of cysLTs. We also examined the mRNA expression and enzyme activity of LTC4 synthase and other LT-synthetic enzymes.

Results: The amount of LTC4 production was 732.0+/-19.0 pg/10(6) cells in DMSO-differentiated HL-60 cells. The value was significantly decreased to 420.7+/-22.7 pg/10(6) cells in the presence of DSCG at 100 microg/ml. The DMSO-induced mRNA expression and enzyme activity of LTC4 synthase was also suppressed by DSCG.

Conclusions: Our results indicate that DSCG suppresses the DMSO-induced LTC4 synthase-activity by inhibiting mRNA expression of LTC4 synthase, which might be a novel anti-allergic action of DSCG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Asthmatic Agents / pharmacology*
  • Cell Differentiation / drug effects
  • Cromolyn Sodium / pharmacology*
  • Cysteine / biosynthesis*
  • Dimethyl Sulfoxide / pharmacology
  • Epoxide Hydrolases / metabolism
  • Glutathione Transferase / metabolism
  • Granulocytes / cytology*
  • HL-60 Cells
  • Humans
  • Leukotrienes / biosynthesis*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Solvents / pharmacology

Substances

  • Anti-Asthmatic Agents
  • Leukotrienes
  • RNA, Messenger
  • Solvents
  • cysteinyl-leukotriene
  • Glutathione Transferase
  • Epoxide Hydrolases
  • leukotriene-C4 synthase
  • Cysteine
  • Cromolyn Sodium
  • leukotriene A4 hydrolase
  • Dimethyl Sulfoxide