Mast cells prevent dexamethasone-induced cell death of cultured fibroblasts: relationship to gap junctional intercellular communications.
BACKGROUND
Dexamethasone, a common therapy for reducing hypertrophic scar, sometimes fails. However, in cell culture, all dexamethasone-treated fibroblasts die. In co-cultures, gap junction intercellular communications between mast cells and fibroblasts promote profibrotic activities. Does the co-culture of mast cells with fibroblasts prevent dexamethasone-induced fibroblast death?


METHODS
Survival of fibroblasts co-cultured with RMC-1 cells, a rat mast cell line, receiving dexamethasone was studied. RMC-1 cells pretreated with a secretagogue that degranulated mast cells and/or with a long-acting gap junction intercellular communications inhibitor were compared to untreated RMC-1 cells co-cultured with fibroblasts and dexamethasone.


RESULTS
Fibroblasts alone treated with dexamethasone all died in 3 hours. Fibroblasts co-cultured with intact RMC-1 cells or with degranulated RMC-1 cells in dexamethasone all survived. No fibroblasts survived, co-cultured with RMC-1 cells unable to form gap junction intercellular communications with fibroblasts.


CONCLUSIONS
Dexamethasone-treated fibroblasts, forming gap junction intercellular communications with mast cells, may explain why dexamethasone therapy sometimes fails. Gap junction intercellular communications between scar mast cells and fibroblasts or myofibroblasts apparently blocks the death of these cell populations. Preventing gap junction intercellular communications between mast cells and fibroblasts by including anti-gap junction intercellular communication agents may enhance the effectiveness of steroid therapy in treating excessive scarring.
Harrisburg and Hershey, Pa. From Leber & Wolf Plastic Surgery Limited; and the Division of Plastic Surgery, Department of Surgery, The Pennsylvania State University, College of Medicine.
Theodore T
TT
Foley
H Paul
HP
Ehrlich
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy / Q000473:pathology; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D052816:Foreskin / Q000166:cytology; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007627:Keloid / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D051381:Rats
D005938:Glucocorticoids; D003907:Dexamethasone