Etanercept suppresses regenerative hyperplasia in psoriasis by acutely downregulating epidermal expression of interleukin (IL)-19, IL-20 and IL-24.
Br J Dermatol
; 167(1): 92-102, 2012 Jul.
Article
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| MEDLINE
| ID: mdl-22458549
ABSTRACT
BACKGROUND:
Psoriasis is a Th17/Th1-mediated skin disease that often responds to antitumour necrosis factor (TNF)-α therapies, such as etanercept.OBJECTIVES:
To better define mechanisms by which etanercept improves psoriasis and to gain insight into disease pathogenesis.METHODS:
We investigated the early biochemical and cellular effects of etanercept on skin lesions in responder patients prior to substantial clinical improvement (≤ 4 weeks).RESULTS:
By 1 week, etanercept acutely suppressed gene expression of the interleukin (IL)-20 subfamily of cytokines (IL-19, IL-20, IL-24), which were found to be predominantly epidermis-derived and which are implicated in stimulating epidermal hyperplasia. Additionally, by 1 week of therapy, suppression of other keratinocyte-derived products (chemokines, antimicrobial proteins) occurred, while suppression of epidermal regenerative hyperplasia occurred within 1-3 weeks. Th17 elements (IL-23p19, IL-12p40, IL-17A, IL-22) were suppressed by 3-4 weeks. In vitro, TNF-α and IL-17A coordinately stimulated the expression of the IL-20 subfamily in normal keratinocytes.CONCLUSIONS:
Based on the rapid suppression of regenerative hyperplasia, chemokines and other keratinocyte-derived products, including the IL-20 subfamily, we propose that epidermal activation is a very early target of etanercept. As many of these keratinocyte markers are stimulated by TNF-α, their rapid downregulation is likely to reflect etanercept's antagonism of TNF-α. Additionally, decreased epidermal hyperplasia might result specifically from acute suppression of the IL-20 subfamily, which is also a likely consequence of etanercept's antagonism of TNF-α. Thus, the IL-20 subfamily has potential importance in the pathogenesis of psoriasis and therapeutic response to etanercept.
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Banco de datos:
MEDLINE
Asunto principal:
Psoriasis
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Inmunoglobulina G
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Antiinflamatorios no Esteroideos
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Interleucinas
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Receptores del Factor de Necrosis Tumoral
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Epidermis
Límite:
Adolescent
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Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Revista:
Br J Dermatol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos