PGD2 induces eotaxin-3 via PPARgamma from sebocytes: a possible pathogenesis of eosinophilic pustular folliculitis.

Authors: Nakahigashi, K  Doi, H  Otsuka, A  Hirabayashi, T  Murakami, M  Urade, Y  Zouboulis, CC  Tanizaki, H  Egawa, G  Miyachi, Y  Kabashima, K 
Citation: Nakahigashi K, etal., J Allergy Clin Immunol. 2012 Feb;129(2):536-43. doi: 10.1016/j.jaci.2011.11.034. Epub 2011 Dec 28.
Pubmed: (View Article at PubMed) PMID:22206772
DOI: Full-text: DOI:10.1016/j.jaci.2011.11.034

BACKGROUND: Eosinophilic 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. OBJECTIVE: To determine the involvement of PGs in the pathogenesis of EPF. METHODS: We performed immunostaining for PG synthases in EPF skin lesions. We examined the effect of PGD(2) on induction of eotaxin, a chemoattractant for eosinophils, in human keratinocytes, fibroblasts, and sebocytes and sought to identify its responsible receptor. RESULTS: Hematopoietic PGD synthase was detected mainly in infiltrating inflammatory cells in EPF lesions, implying that PGD(2) was produced in the lesions. In addition, PGD(2) and its immediate metabolite 15-deoxy-Delta 12,14-PGJ(2) (15d-PGJ(2)) 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. CONCLUSION: The PGD(2)/PGJ(2)-peroxisome proliferator-activated receptor gamma pathway induces eotaxin production from sebocytes, which may explain the massive eosinophil infiltrates observed around pilosebaceous units in EPF.

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CRRD ID: 11081159
Created: 2016-05-26
Species: All species
Last Modified: 2016-05-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.