Impact of IL-13 on Epidermal Inflammation in Atopic Dermatitis

摘要

Background: Skin inflammation in atopic dermatitis (AD) is characterized by lymphocytic infiltration. Recent studies have described that IL-13 acts on epithelial cells via inducing chemokines. In this study we investigated the role of IL-13 stimulated human primary keratinocytes (HPKs) in recruitment of lymphocytes and further delineated the mechanism of enrichment of these cells. Methods: Responsiveness of HPK to 1L-13 was determined by ELISA based detection of secreted chemokines and active matrix metalloproteinase 9 (MMP-9). We performed migration assays with CD4~+ T-cells. Results: We observed preferential migration of CCR4~+ CD4~+ T-cells toward IL-13 stimulated HPKs. Interestingly, CCR4~+ CD4~+ T-cells from AD patients showed a higher chemotactic response than those from healthy individuals. We observed a marked increase in the expression of CCL-22/MDC in IL-13 stimulated HPKs as compared to unstimulated cells. In addition we found that IL-13 stimulated HPKs secreted biologically active MMP-9 which could degrade collagen type IV of the basement membrane. Conclusions: Taken together our data suggest that IL-13 stimulated HPKs participate in enriching Th2-cells in lesional skin of acute AD and facilitate their infiltration into the epidermal compartment by degrading the basement membrane.