Inhibitory effect of retinoic acid on proliferation, maturation and tryptase level in human leukemic mast cells (HMC-1).
Mast cells play important role in allergic inflammation by releasing histamine, tryptase and several inflammatory cytokines. Human leukemic mast cells (HMC-1) have been used to study mast cell mediator and their role in inflammatory mechanisms. HMC-1 contain and release several inflammatory mediators, of which the proteolytic enzyme tryptase is most characteristic. Retinoids, including retinoic acid, are naturally occurring and synthetic derivatives of vitamin A. All-trans-retinoic (ATRA) acid had been previously reported to inhibit cell proliferation, differentiation and apoptosis. In the present study, we investigated the effect of ATRA on the proliferation and secretion of tryptase in HMC-1. HMC-1 were treated with ATRA at 10(-4M), 10(-5M) or 10(-6M) for 3, 4 or 5 days in culture. Control HMC-1 were treated with equal amount of culture medium only. ATRA decreased the number of HMC-1 as compared to the control group. The same treatment for 3, 4 or 5 days also decreased intracellular tryptase levels. These results indicate that ATRA significantly inhibits both proliferation and growth as shown by the decreased intracellular tryptase levels in HMC-1. ATRA may be a useful agent in the treatment of mast cell proliferative disorders.
Alexandrakis
M G
MG
Department of Hematology, University of Crete School of Medicine, University Hospital of Herakleion, Crete, Greece.
Kyriakou
D S
DS
Seretakis
D
D
Boucher
W
W
Letourneau
R
R
Kempuraj
D
D
Theoharides
T C
TC
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007946:Leukemia, Mast-Cell / Q000201:enzymology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D012697:Serine Endopeptidases / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D053802:Tryptases; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D014212:Tretinoin; D012697:Serine Endopeptidases; D053802:Tryptases