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

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 LTC 4, an initial product of cysLTs. We also examined the mRNA expression and enzyme activity of LTC 4 synthase and other LT-synthetic enzymes. Results: The amount of LTC 4 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 μg/ml. The DMSO-induced mRNA expression and enzyme activity of LTC 4 synthase was also suppressed by DSCG. Conclusions: Our results indicate that DSCG suppresses the DMSO-induced LTC 4 synthase-activity by inhibiting mRNA expression of LTC 4 synthase, which might be a novel anti-allergic action of DSCG.