The role angiogenesis plays in atopic dermatitis is not well understood. The authors previously demonstrated ultrastructurally dermal microvascular angiogenesis in the IL-4-transgenic mouse model of atopic dermatitis. Here, they determine the angiogenic factors involved in dermal microvascular angiogenesis, regulatory function of inflammatory cytokines on the VEGF-A production, and microvascular permeability in this model. Computer-assisted photometric analyses for immunofluorescence-labeled CD31 demonstrated a progressive increase in blood vessel number, diameter, and percent dermal areas occupied by CD31(+) vessels as the disease evolves in transgenic mice from before disease onset through early and late skin lesions. Similar findings were documented for VEGR2(+) vessels. Quantification of skin angiogenic factor mRNAs showed progressive increase of transcripts of VEGF-A, but not VEGF-B, VEGF-C, or VEGF-D. ELISA showed a similar increase of VEGF-A in the serum and skin of transgenic mice. IL-6 and IFN-gamma stimulated VEGF-A mRNA production in the skin and in primary keratinocytes of transgenic mice. Other skin angiogenic factors that increased included Ang-1, Ang-2, GBP-1, and VE-cadherin. Microvascular leakage began in the transgenic mouse skin before disease onset and peaked in the late stage. In conclusion, IL-6 and IFN-gamma may play important roles in upregulation of VEGF-A, along with other pro-angiogenic factors, to induce dermal microvascular angiogenesis.

Introduction: Light-emitting diode (LED) therapy uses different wavelengths of light and has been reported to accelerate cutaneous wound healing. Carnosic acid is an antioxidant that is also thought to be photoprotective. We designed an in vitro study to examine the effects of LED and carnosic acid on the proliferation and migration of human keratinocytes. Materials and Methods: Clinically normal human keratinocytes were cultured and exposed to two wavelengths: 620 nm and 660 nm LED at different fluences. In the second part of this study, a different batch of human keratinocytes was grown in culture, and different concentrations of carnosic acid were added. Results: At the two wavelengths that were used, LED did not appear to have any therapeutic effect and was not effective in stimulating keratinocyte proliferation. Exposure to greater energy levels (increased fluence) produced increased cell damage that was directly proportional to the increase in energy. On the other hand, treatment of the cell cultures with the antioxidant carnosic acid resulted in an increase of keratinocyte cell proliferation, and this increase was also proportional to the concentration of carnosic acid. Conclusions: This study did not support the hypothesis that LED treatment results in keratinocyte proliferation; however, carnosic acid, a potent antioxidant, stimulated keratinocyte production and could be implicated in wound healing and rejuvenation.