Mast cells can revert dexamethasone-mediated down-regulation of stem cell factor.
Mast cell hyperplasia can be causally related with chronic inflammation and liver fibrosis. Their survival and proliferation is dependent upon locally produced growth factors, the major one being the stem cell factor (SCF). Glucocorticoids can decrease mastocytosis, down-regulating the mast cell production of pro-inflammatory factors or inhibiting the expression of SCF in stroma. We compared dexamethasone effect on SCF expression in co-cultures of mast cells with NIH/3T3 fibroblasts or with primary cultures of activated hepatic stellate cells. Dexamethasone abrogated the NIH/3T3 stroma capacity to sustain mast cell proliferation, but not of hepatic stellate cells, at the post-transcriptional level. Mast cells reverted completely dexamethasone effect on hepatic stellate cells, increasing their SCF synthesis and transport. In both models, dexamethasone inhibited the mast cell spreading on the stroma, which was thus not required for mast cell survival and proliferation. Liver pathologies associated with mast cell hyperplasia are not expected to be sensitive to glucocorticoid treatments.
Brito
J M
JM
Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-970, Rio de Janeiro, Brazil.
Mermelstein
C S
CS
Tempone
A J
AJ
Borojevic
R
R
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D006099:Granuloma / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019089:Stem Cell Factor / Q000187:drug effects* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D019089:Stem Cell Factor; D003907:Dexamethasone