Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis.
PLoS One
; 12(7): e0181486, 2017.
Article
en En
| MEDLINE
| ID: mdl-28708859
ABSTRACT
BACKGROUND:
Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPß, STAT3 activated by proinflammatory cytokines.OBJECTIVES:
We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation. A-SAA expression was also studied in mouse skin and liver in a model mimicking psoriasis and in the skin and sera of psoriatic and atopic dermatitis (AD) patients.METHODS:
NHEK were stimulated by A-SAA or the cytokines IL-1α, IL-17A, IL-22, OSM, TNF-α alone or in combination, previously reported to reproduce features of psoriasis. Murine skins were treated by imiquimod cream. Human skins and sera were obtained from patients with psoriasis and AD. A-SAA mRNA was quantified by RT qPCR. A-SAA proteins were dosed by ELISA or immunonephelemetry assay.RESULTS:
IL-1α, TNF-α and mainly IL-17A induced A-SAA expression by NHEK. A-SAA induced its own production and the synthesis of hBD2 and CCL20, both ligands for CCR6, a chemokine receptor involved in the trafficking of Th17 lymphocytes. A-SAA expression was increased in skins and livers from imiquimod-treated mice and in patient skins with psoriasis, but not significantly in those with AD. Correlations between A-SAA and psoriasis severity and duration were observed.CONCLUSION:
Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Psoriasis
/
Piel
/
Proteína Amiloide A Sérica
/
Regulación hacia Arriba
/
Interleucina-17
/
Dermatitis Atópica
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Francia