Insulin-like growth factor-I rescue of primary keratinocytes from pre- and post-ultraviolet B radiation effects

Ultraviolet B radiation (UVBR) induces the formation of photolesions in epidermal keratinocytes, potentially affecting cellular function and contributing towards malignant transformation. Insulin-like growth factor-I (IGF-I) contributes to protection of keratinocytes against UVBR-induced damage. Studies have shown that exogenous IGF-I or dermal fibroblast conditioned media pre-UVBR contributes to protection in primary keratinocytes by preventing apoptosis, modulating cell cycle progression and affecting photolesion removal through its damage preventative effects, however, the efficacy of IGF-I post-UVBR has not been sufficiently addressed. Using 2D and 3D photobiology skin models, the ability of IGF-I post-UVBR to rescue primary keratinocytes from photodamage was investigated. The photoprotective effect of IGF-I, both pre- and post-UVBR on cellular functions of irradiated keratinocytes was examined. IGF-I application, either pre- or post-UVBR, was found to alter keratinocyte survival, apoptosis, cell cycle progression and damage removal responses to UVBR. In particular, IGF-I application post-UVBR was found to promote increased keratinocyte survival, prevent apoptosis, shift cell cycle progression and reduce photodamage in all the skin models. Furthermore, marked differences were observed in activation of signalling cascades upon IGF-I treatment post-UVBR. Taken together, these findings indicate that in addition to a previously known photodamage preventative effect, IGF-I treatment post-UVBR has a photoreparative role suggesting it may hold potential in the development of effective remedial strategies against sunburns and photodamage. Graphical summary of the effects of IGF-I pre/post UVBR on primary keratinocytes present in photobiology skin models. Keratinocytes cultured in monolayers, co-cultured with fibroblasts and human skin equivalents were irradiated with selected doses of UVBR and treated with 20 ng/ml IGF-I either pre- or post-UVBR. The effect of IGF-I treatment on critical cellular responses to UVBR was assessed. In summary, IGF-I application, specifically post-UVBR IGF-I treatment was found to alter UVBR responses in keratinocytes cultured in monolayers, co-cultured with fibroblasts and HSEs as represented in terms of effects on cell survival, apoptosis, CPD removal, cell cycle progression and modulation of major signalling mediators. [Display omitted] •2-D co-cultures and 3-D tissue reconstructs of skin are established as model systems.•IGF-I