Transcriptional Characterization of the Effects of Macrophages on Inflammation-Induced Reconstructed Human Skin Equivalents

Recently, artificial skin has been widely used to evaluate the biochemical safety and efficacy of certain drugs. Macrophages play a crucial role in the skin immune response by interacting with fibroblasts and keratinocytes. Transcriptional analysis is a cost-effective method to assess the immune response of macrophages in artificial skin. However, high variability in the mRNA levels of inflammatory factors increases the difficulty of evaluating their immunity against biochemicals. In this study, three-dimensional (3D) artificial skin models were identified to be more sensitive to inflammatory transcription levels than two-dimensional (2D) cultures during the interactions of macrophages, fibroblasts, and keratinocytes. Lipopolysaccharides significantly increased the interleukin ( IL )- 1β and IL-6 levels in 3D fibroblasts/keratinocytes than in 2D culture. They also significantly upregulated IL-1β, IL-6, IL-23 , and tumor necrosis factor-α levels in the 3D macrophage/fibroblast/keratinocyte model. In addition, the macrophage-containing 3D skin was evaluated as a promising model for inflammatory transcriptional analysis via in vitro psoriasis studies using imiquimod.