Unique and synergistic roles for 17beta-estradiol and macrophage migration inhibitory factor during cutaneous wound closure are cell type specific.
The cutaneous wound healing response is complex, comprising numerous overlapping events including inflammation, fibroblast migration, reepithelialization, and wound contraction. With increased age and resultant reduced systemic estrogens, these processes are disrupted and delayed healing ensues. We have demonstrated previously that the proinflammatory cytokine macrophage migration inhibitory factor (MIF) acts as a global regulator of wound healing mediating the majority of estrogen's healing promoting activity. MIF is expressed by numerous wound cell types yet the interaction between estrogens and MIF at the cellular level is still poorly understood. In this study we demonstrate novel accelerated healing in MIF null mice using an excisional wound model. Moreover, we show cell-type-specific differences in the effects of 17beta-estradiol and/or MIF on the cellular function of a range of wound cell types in vitro. Intriguingly, 17beta-estradiol is able to promote the migration of all cell types studied indicating a clear role for cell migration in accelerated wound healing.
Emmerson
Elaine
E
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Campbell
Laura
L
Ashcroft
Gillian S
GS
Hardman
Matthew J
MJ
D000818:Animals; D001706:Biopsy; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004958:Estradiol / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D012867:Skin / Q000473:pathology; D012879:Skin Physiological Phenomena; D014945:Wound Healing / Q000502:physiology*
D004967:Estrogens; D008263:Macrophage Migration-Inhibitory Factors; D004958:Estradiol