Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis - Sorbonne Université Access content directly
Journal Articles PLoS ONE Year : 2017

Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis

François-Xavier Bernard

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/EBPβ, 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.
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Dates and versions

hal-01703911 , version 1 (12-02-2024)

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Elodie Couderc, Franck Morel, Pierre Levillain, Amandine Buffière-Morgado, Magalie Camus, et al.. Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis. PLoS ONE, 2017, 12 (7), pp.e0181486. ⟨10.1371/journal.pone.0181486⟩. ⟨hal-01703911⟩
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