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


CONCLUSIONS
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.
Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kyoko
K
Nakahigashi
Hiromi
H
Doi
Atsushi
A
Otsuka
Tetsuya
T
Hirabayashi
Makoto
M
Murakami
Yoshihiro
Y
Urade
Christos C
CC
Zouboulis
Hideaki
H
Tanizaki
Gyohei
G
Egawa
Yoshiki
Y
Miyachi
Kenji
K
Kabashima
D000813:Anilides / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology; D004804:Eosinophils / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D005499:Folliculitis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000276:immunology* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology; D012627:Sebaceous Glands / Q000166:cytology / Q000276:immunology*; D012872:Skin Diseases, Vesiculobullous / Q000276:immunology* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D014162:Transfection
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C533609:CAY 10471; C120429:CCL26 protein, human; D002227:Carbazoles; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D006827:Hydantoins; D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C058848:BW A868C; C034832:13,14-dihydro-15-ketoprostaglandin D2; C030669:BW 245C; D015230:Prostaglandin D2