The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis.
BACKGROUND
Interleukin (IL)-20 and IL-19 are recently discovered members of the IL-10 family of cytokines. The skin of transgenic mice overexpressing IL-20 shows histological changes resembling some of those seen in psoriasis, i.e. thickened epidermis, hyperkeratosis and a compact stratum corneum. IL-19 and IL-20, as well as their receptor complexes, IL-20Ralpha/IL-20Rbeta and IL-22Ralpha/IL-20Rbeta, are expressed in human skin.


OBJECTIVE
To study the dynamics of IL-19 and IL-20 gene expression as well as the expression of their receptor subunits in psoriatic skin lesions.


METHODS
Punch biopsies from patients with plaque-type psoriasis were collected before, during and after 28 days of treatment with either calcipotriol or ciclosporin (CsA). IL-20, IL-19, IL-20Ralpha, IL-20Rbeta and IL-22Ralpha mRNA expression were determined by quantitative reverse transcriptase-polymerase chain reaction.


RESULTS
We found IL-19 and IL-20 mRNA expression in lesional psoriatic skin to be strongly upregulated compared with nonlesional psoriatic skin by a factor of 65 and 22, respectively. In contrast to previous reports, IL-20Ralpha and IL-20Rbeta mRNA levels showed a modest but statistically significant decrease in lesional psoriatic skin compared with nonlesional psoriatic skin. During treatment with calcipotriol or CsA, IL-19 and IL-20 mRNA levels decrease in accordance with the clinical improvement of psoriasis. Neither IL-19, IL-20, nor receptor subunit mRNA expression in lesional psoriatic skin reaches the levels of nonlesional skin during this short-term treatment. These findings are in line with the residual disease activity observed at the end of treatment.


CONCLUSIONS
The increased IL-19 and IL-20 mRNA expression levels in lesional psoriatic skin suggest that these two cytokines play a role in the pathogenesis of psoriasis. An imbalance in the receptor complexes for IL-19 and IL-20 might contribute to their suspected pathogenic effects.
Otkjaer
K
K
Department of Dermatology, Aarhus Hospital, P.P. Ørumsgade 11, University of Aarhus, DK-8000 Aarhus C, Denmark. otkjaer@ki.au.dk
Kragballe
K
K
Funding
A T
AT
Clausen
J T
JT
Noerby
P L
PL
Steiniche
T
T
Iversen
L
L
D000328:Adult; D000368:Aged; D002117:Calcitriol / Q000031:analogs & derivatives / Q000627:therapeutic use; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000627:therapeutic use; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000378:metabolism
D003879:Dermatologic Agents; C421250:IL19 protein, human; D007166:Immunosuppressive Agents; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; C492510:interleukin-20 receptor; C415369:interleukin-22 receptor; D016753:Interleukin-10; C055085:calcipotriene; D016572:Cyclosporine; D002117:Calcitriol; C422042:interleukin 20