Disodium cromoglycate suppresses the induction of cysteinyl leukotriene synthesis during granulocytic differentiation in HL-60 cells.
OBJECTIVE
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.
Zaitsu
Masafumi
M
Department of pediatrics, Faculty of Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. zaitsum@post.saga-med.ac.jp
Honjo
Kinji
K
Ishii
Eiichi
E
Hamasaki
Yuhei
Y
D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004205:Cromolyn Sodium / Q000494:pharmacology*; D003545:Cysteine / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology*; D018922:HL-60 Cells; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012997:Solvents / Q000494:pharmacology
D018927:Anti-Asthmatic Agents; D015289:Leukotrienes; D012333:RNA, Messenger; D012997:Solvents; C112381:cysteinyl-leukotriene; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C041116:leukotriene-C4 synthase; D003545:Cysteine; D004205:Cromolyn Sodium; C043134:leukotriene A4 hydrolase; D004121:Dimethyl Sulfoxide