Identification of a novel receptor for S100A8 and its possible involvement in abnormal proliferation

Although S100A8 and S100A9 are suggested to play important roles in inflammation, molecular mechanisms are still obscure. Previously we reported that S100A9 induced inflammatory cytokines including IL-8 and TNFα and S100A8 promoted proliferation in cultured keratinocytes. Using LC/MS/MS analysis we identified matrix metalloproteinase inducer (EMMPRIN) as a specific receptor for S100A9. In the present study, we tried to find a receptor for S100A8. Database search based on the similarity with EMMPRIN identified neuroplastin (NPTN) as a candidate molecule. We confirmed that NPTN was bound with S100A8 by immunoprecipitation and ELISA assays. Externally added S100A8 promoted keratinocyte proliferation and it was significantly suppressed by the knockdown of NPTN. Interestingly similar results were obtained by using EMMPRIN siRNA. Since S100A8 and S100A9 are capable to form a heterodimer (calprotectin), these results may suggest that NPTN also makes a heterodimer with EMMPRIN. We found that NPTN was able to make a heterodimer with EMMPRIN as well as a homodimer by themselves. Immunohistochemical analysis demonstrated that NPTN and EMMPRIN were expressed in the lesional skin with atopic dermatitis (AD), whereas they could not be detected in the normal skin. Proximity ligation assay indicated that S100A8 and NPTN, or NPTN and EMMPRIN interact together in the lesional skin in vivo. Quantitative comparison between normal and AD skin (n=20) using calprotectin ELISA assays showed that co...
Source: Journal of Dermatological Science - Category: Dermatology Authors: Tags: Abstracts from the 37th Annual Meeting of the Japanese Society for Investigative Dermatology Source Type: research