Speaker
Description
Introduction: S100A8 and S100A9, also known as myeloid-related protein-8 (MRP8) and MRP14, are damage-associated molecular pattern molecules (DAMPs). Both proteins are highly up-regulated in autoimmune diseases of human skin like psoriasis as well as in certain in vivo models (e.g. Imiquimod induced psoriasis like phenotype).
Methods: Keratinocytes collected from adult tail skin of either wildtype or S100A9-/- mice were differentiated under high calcium conditions (1 mM CaCl2). Furthermore keratinocytes of both mice strains were stimulated with different inflammatory mediators. Cells were harvested at different time points and analysis of gene or protein expression was performed.
Results: Both, wildtype and S100A9-/- cells, show a typical expression pattern of genes responsible for differentiation. During differentiation an increased gene expression of both S100 proteins could be detected in wildtype but not in S100A9-/- (here only S100A8) cells. On protein level S100A9-/- cells show no expression of S100A8 and S100A9 whereas wildtype cells express both proteins in increasing amounts during differentiation. Wildtype keratinocytes stimulated with IL-1α, IL-17A, IL-17F, TNFα and Flagellin show a significant elevation of S100A8 and S100A9 on mRNA and protein level compared to unstimulated or IL-13 treated cells.
Conclusion: Both wildtype and S100A9-/- keratinocytes show the same gene expression pattern of proteins known for differentiation, indicating no direct correlation of S100 proteins and keratinocyte differentiation. Surprisingly S100A9-/- keratinocytes do not express S100A8 although mRNA level were increasing during differentiation and stimulation with inflammatory mediators. These results indicate an inflammation and differentiation dependent mechanism of S100 protein expression.
