PGD₂ induces eotaxin-3 via PPAR¦Ã from sebocytes: A?possible pathogenesis of eosinophilic pustular folliculitis

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• 作者：Kyoko Nakahigashi ; MD^a ; Hiromi Doi ; MS^a ; Atsushi Otsuka ; MD ; PhD^a ; Tetsuya Hirabayashi ; PhD^b ; Makoto Murakami ; PhD^b ; Yoshihiro Urade ; PhD^c ; Hideaki Tanizaki ; MD ; PhD^a ; Gyohei Egawa ; MD ; PhD^a ; Yoshiki Miyachi ; MD ; PhD^a ; Kenji Kabashima ; MD ; PhD^a ; ^{kaba@kuhp.kyoto-u.ac.jp}
• 关键词：Prostaglandin D2 ; hematopoietic prostaglandin D synthase ; eotaxin-3/CCL26 ; sebocyte ; peroxisome proliferator&ndash ; activated receptor gamma
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：February, 2012
• 年：2012
• 卷：129
• 期：2
• 页码：536-543
• 全文大小：1270 K

文摘

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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 PGD₂ 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 PGD₂ was produced in the lesions. In addition, PGD₂ and its immediate metabolite 15-deoxy-¦¤ 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.

Conclusion

The 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.