557 A case of acquired dermal melanocytosis associated with Imatinib mesylate treatment

Abstract

Wrinkling has been attributed to the cumulative effects of acute Ultraviolet Radiation (UVR) exposure on the dermis. Previous studies have shown that the collagenase MMP-1 is secreted by dermal fibroblasts and degrades collagen immediately after UV exposure. However, skin ages gradually, and not intermittently after sun exposure. In this study we sought to examine the mechanism underpinning the gradual appearance of wrinkles, and to determine whether this is a result of intrinsic changes in the biology of the dermis. In vitro studies were performed using patient-derived human dermal fibroblasts from healthy skin, HFF and HDF cell lines. Cell lines were UV-protected or repeatedly exposed to UVB. Dermal fibroblasts from fairer skin types had higher levels of UV-induced mutations which, in multivariate analysis, was linked to higher expression of extracellular matrix degradation genes. This suggests that the background UVR exposure history influences the composition of the dermis as it ages. We investigated the mechanism driving collagen degradation in dermal fibroblasts with and without a history of UV damage. Fibroblasts with high background UV exposure have elevated levels of MMP-1 at rest. In addition, they show increased collagen degradation activity, which persists in the absence of acute UV exposure. Our study shows that dermal fibroblasts with a history of chronic UV exposure have higher levels of collagenase expression and activity, even in the absence of acute UV exposure. Importantly, these findings explain the mechanism driving gradual collagen degradation and wrinkling in the absence of UV light.