Leukocyte-derived koebnerisin (S100A15) and psoriasin (S100A7) are systemic mediators of inflammation in psoriasis

被引:59
作者
Batycka-Baran, Aleksandra [1 ,2 ]
Hattinger, Eva [2 ]
Zwicker, Stephanie [2 ]
Summer, Burkhard [2 ]
Howard, O. M. Zack [3 ]
Thomas, Peter [2 ]
Szepietowski, Jacek C. [1 ]
Ruzicka, Thomas [2 ]
Prinz, Joerg C. [2 ]
Wolf, Ronald [2 ]
机构
[1] Wroclaw Med Univ, Dept Dermatol Venereol & Allergol, Wroclaw, Poland
[2] Univ Munich, Dept Dermatol & Allergol, Munich, Germany
[3] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA
关键词
S100; Psoriasin; Koebnerisin; Psoriasis; UVB; Leukocytes; NECROSIS-FACTOR-ALPHA; MOLECULAR-CLONING; PROTEIN PSORIASIN; GENE-EXPRESSION; SKIN; PATHOGENESIS; ULTRAVIOLET; INTERFERES; CYTOKINES; DISEASES;
D O I
10.1016/j.jdermsci.2015.05.007
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background: Psoriasis is a systemic immune-mediated chronic inflammatory disease. In the skin, the antimicrobial proteins koebnerisin (S100A15) and psoriasin (S100A7) are overexpressed in the epidermis of psoriatic lesions and mediate inflammation as chemoattractants for immune cells. Their role for systemic inflammation in circulating leukocytes is unknown. Objective: The aim of the study was to identify circulating leukocyte populations as a source of koebnerisin and psoriasin. Further, immune-stimulatory effects of these S100A proteins on circulating leukocytes were evaluated and their role as therapeutic response markers in patients with psoriasis was analyzed upon UVB treatment. Methods: The expression and production of koebnerisin and psoriasin by leukocytes were assessed by quantitative real-time PCR (qRT-PCR) and immunoblotting.The S100A protein mediated regulation of proinflammatory cytokines by peripheral blood mononuclear cells (PBMCs) was measured with qRT-PCR and cytometric bead assay. Results: We identified circulating leukocytes as novel sources of koebnerisin (S100A15) and psoriasin (S100A7). Circulating leukocytes (PBMCs) of patients with psoriasis produced increased levels of koebnerisin and psoriasin compared to healthy individuals. Both S100A proteins further acted as 'alarmins' on PBMC to induce proinflammatory cytokines implicated in the pathogenesis of psoriasis, such as IL-1 beta TNF-alpha, IL-6 and IL-8. Koebnerisin levels were suppressed in PBMC of psoriatic patients when effectively treated with narrow-band UVB. Conclusions: Data suggest that koebnerisin and psoriasin are systemic pro-inflammatory mediators and koebnerisin acts as a therapeutic response marker in psoriasis. (C) 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:214 / 221
页数:8
相关论文
共 33 条
[11]   S100 proteins in the epidermis [J].
Eckert, RL ;
Broome, AM ;
Ruse, M ;
Robinson, N ;
Ryan, D ;
Lee, K .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2004, 123 (01) :23-33
[12]   Psoriasis: rationale for targeting interleukin-17 [J].
Girolomoni, G. ;
Mrowietz, U. ;
Paul, C. .
BRITISH JOURNAL OF DERMATOLOGY, 2012, 167 (04) :717-724
[13]   INTERLEUKIN-6 IS EXPRESSED IN HIGH-LEVELS IN PSORIATIC SKIN AND STIMULATES PROLIFERATION OF CULTURED HUMAN KERATINOCYTES [J].
GROSSMAN, RM ;
KRUEGER, J ;
YOURISH, D ;
GRANELLIPIPERNO, A ;
MURPHY, DP ;
MAY, LT ;
KUPPER, TS ;
SEHGAL, PB ;
GOTTLIEB, AB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (16) :6367-6371
[14]   The immune system in atherosclerosis [J].
Hansson, Goran K. ;
Hermansson, Andreas .
NATURE IMMUNOLOGY, 2011, 12 (03) :204-212
[15]   Vitamin D Analog Calcipotriol Suppresses the Th17 Cytokine-Induced Proinflammatory S100 "Alarmins" Psoriasin (S100A7) and Koebnerisin (S100A15) in Psoriasis [J].
Hegyi, Zuzana ;
Zwicker, Stephanie ;
Bureik, Daniela ;
Peric, Mark ;
Koglin, Sarah ;
Batycka-Baran, Aleksandra ;
Prinz, Joerg C. ;
Ruzicka, Thomas ;
Schauber, Juergen ;
Wolf, Ronald .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2012, 132 (05) :1416-1424
[16]   Psoriasis - recent advances in understanding its pathogenesis and treatment [J].
Krueger, G ;
Ellis, CN .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2005, 53 (01) :S94-S100
[17]   Narrowband Ultraviolet B Interferes with Gene Expression in the Peripheral Blood T Cells of Patients with Psoriasis [J].
Li, Junqin ;
Hou, Ruixia ;
Yang, Yuanwen ;
Liu, Ruifeng ;
Zhao, Xincheng ;
Li, Xinhua ;
Yin, Guohua ;
An, Peng ;
Wang, Yong ;
Zhang, Kaiming .
DERMATOLOGY, 2013, 226 (02) :128-137
[18]   Pathogenesis and therapy of psoriasis [J].
Lowes, Michelle A. ;
Bowcock, Anne M. ;
Krueger, James G. .
NATURE, 2007, 445 (7130) :866-873
[19]   MOLECULAR-CLONING, OCCURRENCE, AND EXPRESSION OF A NOVEL PARTIALLY SECRETED PROTEIN PSORIASIN THAT IS HIGHLY UP-REGULATED IN PSORIATIC SKIN [J].
MADSEN, P ;
RASMUSSEN, HH ;
LEFFERS, H ;
HONORE, B ;
DEJGAARD, K ;
OLSEN, E ;
KIIL, J ;
WALBUM, E ;
ANDERSEN, AH ;
BASSE, B ;
LAURIDSEN, JB ;
RATZ, GP ;
CELIS, A ;
VANDEKERCKHOVE, J ;
CELIS, JE .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1991, 97 (04) :701-712
[20]   Antimicrobial peptides in the pathogenesis of psoriasis [J].
Morizane, Shin ;
Gallo, Richard L. .
JOURNAL OF DERMATOLOGY, 2012, 39 (03) :225-230