Effects of five commonly used glucocorticoids on haemangioma in vitro.
1. High-dose systemic or intralesional steroids are the first-line pharmacological treatments for haemangioma. However, the mechanism of action of steroids is unknown. Using the in vitro model developed by us, the present study examined some of the effects of five commonly used glucocorticoids on haemangioma biopsies taken from two patients. 2. At 12 micro mol/L, triamcinolone and dexamethasone consistently exhibited capillary growth inhibition, whereas methylprednisolone displayed an inhibitory effect during the first 7 days of culture. At this concentration, inhibition of capillary growth was observed in betamethasone-treated cultures derived from one patient but not in those derived from the other. However, hydrocortisone had a negligible effect on capillary growth. 3. Transcription of various factors considered important for haemangioma development were studied by reverse transcription-polymerase chain reaction. Neither vascular endothelial growth factor nor fibroblast growth factor-2 played a vital role in steroid-induced inhibition of capillary growth. All glucocorticoids induced a marked decrease of interleukin (IL)-6 transcripts. 4. Capillary growth inhibition in cultures treated with all glucocorticoids, except triamcinolone, was associated with an increased transcription of clusterin/apolipoprotein J (clust/apoJ), an apoptotic gene. There was increased transcription of mitochondrial cytochrome (cyt) b in the inhibited cultures resulting from triamcinolone, dexamethasone or methylprednisolone treatment that was associated with capillary growth inhibition, suggesting an important role of mitochondria in glucocorticoid-induced regression of haemangioma. 5. Our results indicate that glucocorticoids may modulate haemangiogenesis via an upregulation of cyt b, clust/apoJ and/or IL-6. The variable effects of different glucocorticoids on one or more of these factors may explain the interindividual variation in the in vivo response of haemangioma to the steroids.
Hasan
Q
Q
Centre for the Study and Treatment of Vascular Birthmarks, Maxillofacial and Burns Unit, Hutt Hospital, Reconstructive Plastic Surgery Research Institute of New Zealand, Wellington, New Zealand.
Tan
S T
ST
Xu
B
B
Davis
P F
PF
D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000235:genetics; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006391:Hemangioma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D043925:Angiogenesis Inducing Agents; D005938:Glucocorticoids