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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:129

Article

Nakahigashi, Kyoko¹  Doi, Hiromi¹  Otsuka, Atsushi¹  Hirabayashi, Tetsuya²  Murakami, Makoto²  Urade, Yoshihiro³  Tanizaki, Hideaki¹  Egawa, Gyohei¹  Miyachi, Yoshiki¹  Kabashima, Kenji¹ 

[1] Kyoto Univ, Dept Dermatol, Grad Sch Med, Kyoto 6068507, Japan

[2] Tokyo Metropolitan Inst Med Sci, Lipid Metab Project, Tokyo 113, Japan

[3] Osaka Biosci Inst, Dept Mol Behav Biol, Osaka, Japan

关键词: Prostaglandin D-2;    hematopoietic prostaglandin D synthase;    eotaxin-3/CCL26;    sebocyte;    peroxisome proliferator-activated receptor gamma;   

DOI  :  10.1016/j.jaci.2011.11.034

来源: Elsevier

【 摘 要 】

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 PG Delta(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. (J Allergy Clin Immunol 2012;129:536-43.)

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