Kerstin Wolk1, Yvonne Frambach2, Arnd Jacobi3, Dagmar Wilsmann-Theis4, Sandra Phillipp5, Ellen Witte-Händel6, Jörg Wenzel4, Rotraut Mössner7, Robert Sabat6. 1. Psoriasis Research and Treatment Centre, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Berlin-Brandenburg Centre for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: kerstin.wolk@charite.de. 2. Department of Dermatology, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. 3. Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. 4. Department of Dermatology and Allergy, University Medical Center, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. 5. Psoriasis Research and Treatment Centre, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. 6. Psoriasis Research and Treatment Centre, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. 7. Department of Dermatology, Georg-August-University Goettingen, Robert-Koch-Straße 40, 37075 Goettingen, Germany.
Abstract
BACKGROUND: Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles. OBJECTIVE: To identify and characterize pathogenetic players in PPP. METHODS: Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry. RESULTS: Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1β and further enhanced by IL-17 and TNF-α, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1β and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin. CONCLUSIONS: In PPP, increased blood levels of LCN2 indicate an important activity of IL-1β in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk.
BACKGROUND:Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles. OBJECTIVE: To identify and characterize pathogenetic players in PPP. METHODS: Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry. RESULTS: Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1β and further enhanced by IL-17 and TNF-α, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1β and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin. CONCLUSIONS: In PPP, increased blood levels of LCN2 indicate an important activity of IL-1β in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk.
Authors: Kristina Navrazhina; Sandra Garcet; Juana Gonzalez; David Grand; John W Frew; James G Krueger Journal: J Invest Dermatol Date: 2021-03-22 Impact factor: 7.590