PGD2 induces eotaxin-3 via PPARγ from sebocytes: A possible pathogenesis of eosinophilic pustular folliculitis

BackgroundEosinophilic pustular folliculitis (EPF) is a chronic intractable pruritic dermatosis characterized by massive eosinophil infiltrates involving the pilosebaceous units. Recently, EPF has been regarded as an important clinical marker of HIV infection, and its prevalence is increasing in number. The precise mechanism by which eosinophils infiltrate into the pilosebaceous units remains largely unknown. Given that indomethacin, a COX inhibitor, can be successfully used to treat patients with EPF, we can assume that COX metabolites such as prostaglandins (PGs) are involved in the etiology of EPF.ObjectiveTo determine the involvement of PGs in the pathogenesis of EPF.MethodsWe performed immunostaining for PG synthases in EPF skin lesions. We examined the effect of PGD2 on induction of eotaxin, a chemoattractant for eosinophils, in human keratinocytes, fibroblasts, and sebocytes and sought to identify its responsible receptor.ResultsHematopoietic PGD synthase was detected mainly in infiltrating inflammatory cells in EPF lesions, implying that PGD2 was produced in the lesions. In addition, PGD2 and its immediate metabolite 15-deoxy-Δ 12,14-PGJ2 (15d-PGJ2) induced sebocytes to produce eotaxin-3 via peroxisome proliferator–activated receptor gamma. Consistent with the above findings, eotaxin-3 expression was immunohistochemically intensified in sebaceous glands of the EPF lesions.ConclusionThe PGD2/PGJ2-peroxisome proliferator–activated receptor gamma pathway induces eotaxin production from sebocytes, which may explain the massive eosinophil infiltrates observed around pilosebaceous units in EPF.