Enhancement of macrophage migration inhibitory factor (MIF) expression in injured epidermis and cultured fibroblasts

After the cDNA of human macrophage migration inhibitory factor (MIF) was cl oned in 1989, this protein has been reevaluated as a pro-inflammatory cytok ine, pituitary hormone and glucocorticoid-induced immunoregulatory protein. We previously reported the expression of MIF in the basal cell layers of t he epidermis, but its pathophysiological function in the skin has not been well understood. In this study, we examined the expression of MIF during th e wound healing of rat skin injured by excision. Reverse transcription-poly merase chain reaction in combination with Southern blot analysis revealed t hat the increase of MIF mRNA expression was biphasic. The maximum peaks wer e observed at 3 and 24 h after the injury. Similarly, maximal increases of the serum MIF level were observed at 3 and 24 h after the injury. Immunohis tochemical analysis at 12 h after injury demonstrated enhanced expression o f MIF protein in the whole epidermal lesion of the wound tissue. By the Boy den chamber assay, we demonstrated that MIF had a chemotactic effect on fre shly prepared keratinocytes from rat skin. Additionally, cultured fibroblas ts from the skill wound lesion secreted a higher amount of MIF in response to lipopolysaccharide compared to those of the normal skin. Furthermore, ad ministration of anti-MIF antibodies induced a delay of wound healing in viv o. Taken together, these results suggest that MIF contributes to the wound healing process of skin tissue. (C) 2000 Elsevier Science B.V. All rights r eserved.