Role of melanoma growth stimulatory activity (MGSA/gro) on keratinocyte function in wound healing.

Abstract

Melanoma growth stimulatory activity/gro alpha (MGSA), a member of the alpha-chemokine family, is produced by a variety of dermal and epidermal cells and can act in a paracrine and autocrine fashion. However, little is known about the importance of MGSA in wound healing. In this study, we quantified the levels of MGSA protein in burn blister and donor site wound fluids. We studied the effects of MGSA on proliferation and migration of primary human keratinocytes and modulation of their integrin expression. Blister fluids contained 0.79 ng/ml (range 0.018 to 4.86 ng/ml) MGSA. Substantial increasing amounts of MGSA were found in donor site fluids from day 1 through day 5 with mean levels ranging from 1.77 to 103 ng/ml at postoperative day 5, which correlated with increasing amounts of tumor necrosis factor alpha (r = 0.86), a known stimulus for MGSA production. In vitro proliferation experiments revealed a maximum stimulation (2.6-fold) with 10 ng/ ml MGSA for 7 days over unstimulated keratinocyte controls; the ED50 was 0.2 ng/ml. DNA content analysis revealed an increase in S phase with 10 ng/ml MGSA stimulation. In cultured keratinocytes, MGSA enhanced the mean fluorescence intensity for alpha 6, while no significant change was seen for beta 1, alpha 2 and alpha 5. We also studied the effect of topically applied MGSA (50 ng/cm2) on the healing of meshed split-thickness human skin grafts on athymic mice. In these wounds, MGSA stimulated the rate of epithelialization (P < 0.05) at day 7, and an increased proportion of mitotic keratinocytes was observed. Wound contraction was significantly (P < 0.05) reduced on days 7 and 14 in the MGSA-treated group. These results suggest that MGSA participates in wound healing by stimulating keratinocyte proliferation.