Decreases in 15-lipoxigenase metabolites in Olmsted syndrome model rats

Infiltration of mast cells, eosinophils, and neutrophils and an increase in fibrotic region were detected in unaffected skin area of Ht rats. Among ~600 lipid species examined, levels of 15-lipoxygenase (LOX) metabolites, the precursors of anti-inflammatory and pro-resolving lipid mediators, and dihydroceramides were decreased by =16-fold in Ht rats compared to wild type rats. Consistent with the decreases in the 15-LOX metabolites, expression levels of the 15-LOXs, Alox15 and Alox15b, were largely reduced. On the other hand, expression levels of the cytokines/chemokines Il36b, Ccl20, Cxcl1, and Cxcl2 and those of the Ca2+-binding proteins S100a8 and S100a9, which are implicated in epidermal proliferation, were increased. The pro-inflammatory state of Ht rats caused by decreases in 15-LOX metabolites and increases in cytokines/chemokines may contribute to the pathogenesis of OS.