Epidermal overexpression of interleukin-19 and-20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine A or calcipotriol

被引:141
作者
Romer, J
Hasselager, E
Norby, PL
Steiniche, T
Clausen, JT
Kragballe, K
机构
[1] Novo Nordisk AS, Discovery, DK-2880 Bagsvaerd, Denmark
[2] Aarhus Kommune Hosp, DK-8000 Aarhus, Denmark
[3] Marselisborg Hosp, Dept Dermatol, DK-8000 Aarhus, Denmark
关键词
inflammation; interleukin-19; interleukin-20; interleukin-24; keratinocytes; psoriatic plaque;
D O I
10.1111/j.1523-1747.2003.12626.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Interleukin-19, 20, and 24 are new members of the IL-10 family binding and signaling through the IL-20R1/IL-20R2 heterodimer, while IL-20 and 24 also bind to the IL-20R2/IL-22R1 heterodimer. Using in situ hybridization we have studied mRNA expression of IL-19, 20, and 24 and their related receptor chains in skin from psoriatic patients before and during short-term treatment with either oral cyclosporine A or topical calcipotriol. In untreated lesions IL-19 and IL-20 mRNA was expressed focally in epidermis above the dermal papillae, whereas IL-24 was expressed in mononuclear cells in the dermal infiltrate. The expression of IL-19 and 20 mRNA was confined to the basal and suprabasal keratinocytes. No expression of IL-19 and 20 mRNA could be detected in uninvolved psoriatic skin. Treatment with cyclosporine A and calcipotriol resulted in disappearance of the IL-19 and 20 mRNA. Expression of mRNA for the receptor chains IL-20R1 and IL-20R2 was found throughout the psoriatic epidermal layer, whereas IL-22R1 mRNA was predominantly expressed in the superficial part of the psoriatic epidermis. These findings show that IL-19 and IL-20 are synthesized by a distinct population of keratinocytes. It remains to be clarified whether IL-19 and IL-20 are implicated in the pathogenesis of psoriasis.
引用
收藏
页码:1306 / 1311
页数:6
相关论文
共 24 条
[1]   Interleukin 20: Discovery, receptor identification, and role in epidermal function [J].
Blumberg, H ;
Conklin, D ;
Xu, WF ;
Grossmann, A ;
Brender, T ;
Carollo, S ;
Eagan, M ;
Foster, D ;
Haldeman, BA ;
Hammond, A ;
Haugen, H ;
Jelinek, L ;
Kelly, JD ;
Madden, K ;
Maurer, MF ;
Parrish-Novak, J ;
Prunkard, D ;
Sexson, S ;
Sprecher, C ;
Waggie, K ;
West, J ;
Whitmore, TE ;
Yao, L ;
Kuechle, MK ;
Dale, BA ;
Chandrasekher, YA .
CELL, 2001, 104 (01) :9-19
[2]   The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24 [J].
Caudell, EG ;
Mumm, JB ;
Poindexter, N ;
Ekmekcioglu, S ;
Mhashilkar, AM ;
Yang, XHH ;
Retter, MW ;
Hill, P ;
Chada, S ;
Grimm, EA .
JOURNAL OF IMMUNOLOGY, 2002, 168 (12) :6041-6046
[3]   Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial [J].
Chaudhari, U ;
Romano, P ;
Mulcahy, LD ;
Dooley, LT ;
Baker, DG ;
Gottlieb, AB .
LANCET, 2001, 357 (9271) :1842-1847
[4]   Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types [J].
Dumoutier, L ;
Leemans, C ;
Lejeune, D ;
Kotenko, SV ;
Renauld, JC .
JOURNAL OF IMMUNOLOGY, 2001, 167 (07) :3545-3549
[5]   CYCLOSPORINE FOR PLAQUE-TYPE PSORIASIS - RESULTS OF A MULTIDOSE, DOUBLE-BLIND TRIAL [J].
ELLIS, CN ;
FRADIN, MS ;
MESSANA, JM ;
BROWN, MD ;
SIEGEL, MT ;
HARTLEY, AH ;
ROCHER, LL ;
WHEELER, S ;
HAMILTON, TA ;
PARISH, TG ;
ELLISMADU, M ;
DUELL, E ;
ANNESLEY, TM ;
COOPER, KD ;
VOORHEES, JJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (05) :277-284
[6]   The interleukin-10 family of cytokines [J].
Fickenscher, H ;
Hör, S ;
Küpers, H ;
Knappe, A ;
Wittmann, S ;
Sticht, H .
TRENDS IN IMMUNOLOGY, 2002, 23 (02) :89-96
[7]   Immunomodulation by interleukin-10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in psoriasis [J].
Friedrich, M ;
Döcke, WD ;
Klein, A ;
Philipp, S ;
Volk, HD ;
Sterry, W ;
Asadullah, K .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 118 (04) :672-677
[8]   Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease [J].
Ghoreschi, K ;
Thomas, P ;
Breit, S ;
Dugas, M ;
Mailhammer, R ;
van Eden, W ;
van der Zee, R ;
Biedermann, T ;
Prinz, J ;
Mack, M ;
Mrowietz, U ;
Christophers, E ;
Schlöndorff, D ;
Plewig, G ;
Sander, CA ;
Röcken, M .
NATURE MEDICINE, 2003, 9 (01) :40-46
[9]   A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta [J].
Gruenberg, BH ;
Schoenemeyer, A ;
Weiss, B ;
Toschi, L ;
Kunz, S ;
Wolk, K ;
Asadullah, K ;
Sabat, R .
GENES AND IMMUNITY, 2001, 2 (06) :329-334
[10]   Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties [J].
Huang, EY ;
Madireddi, MT ;
Gopalkrishnan, RV ;
Leszczyniecka, M ;
Su, ZZ ;
Lebedeva, IV ;
Kang, DC ;
Jiang, HP ;
Lin, JJ ;
Alexandre, D ;
Chen, YM ;
Vozhilla, N ;
Mei, MX ;
Christiansen, KA ;
Sivo, F ;
Goldstein, NI ;
Mhashilkar, AB ;
Chada, S ;
Huberman, E ;
Pestka, S ;
Fisher, PB .
ONCOGENE, 2001, 20 (48) :7051-7063