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

Publisher: Mosby Country of Publication: United States NLM ID: 1275002 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6825 (Electronic) Linking ISSN: 00916749 NLM ISO Abbreviation: J Allergy Clin Immunol Subsets: MEDLINE

Original Publication: St Louis, Mosby.

Chemokines, CC/*immunology ; Eosinophilia/*immunology ; Folliculitis/*immunology ; PPAR gamma/*immunology ; Prostaglandin D2/*immunology ; Sebaceous Glands/*immunology ; Skin Diseases, Vesiculobullous/*immunology; Anilides/pharmacology ; Carbazoles/pharmacology ; Cell Line ; Cells, Cultured ; Chemokine CCL26 ; Chemokines, CC/genetics ; Eosinophilia/pathology ; Eosinophils/immunology ; Fibroblasts/immunology ; Folliculitis/pathology ; Humans ; Hydantoins/pharmacology ; Keratinocytes/immunology ; PPAR gamma/antagonists & inhibitors ; PPAR gamma/genetics ; Prostaglandin D2/analogs & derivatives ; Prostaglandin D2/pharmacology ; RNA, Messenger/metabolism ; RNA, Small Interfering/genetics ; Receptors, Prostaglandin/agonists ; Receptors, Prostaglandin/antagonists & inhibitors ; Receptors, Prostaglandin/immunology ; Sebaceous Glands/cytology ; Skin Diseases, Vesiculobullous/pathology ; Sulfonamides/pharmacology ; Transfection

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.
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.
(Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Erratum in: J Allergy Clin Immunol. 2014 Feb;133(2):604. Zouboulis, Christos C [added].

0 (2-chloro-5-nitrobenzanilide)
0 (Anilides)
0 (CAY 10471)
0 (CCL26 protein, human)
0 (Carbazoles)
0 (Chemokine CCL26)
0 (Chemokines, CC)
0 (Hydantoins)
0 (PPAR gamma)
0 (RNA, Messenger)
0 (RNA, Small Interfering)
0 (Receptors, Prostaglandin)
0 (Sulfonamides)
118675-50-6 (BW A868C)
59894-07-4 (13,14-dihydro-15-ketoprostaglandin D2)
75693-75-3 (BW 245C)
RXY07S6CZ2 (Prostaglandin D2)

Eosinophilic pustular folliculitis

Date Created: 20111231 Date Completed: 20120412 Latest Revision: 20171116

20240829

10.1016/j.jaci.2011.11.034

22206772