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

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.

• Authors: Elodie Couderc, Franck Morel, Pierre Levillain, Amandine Buffière-Morgado, Magalie Camus, Camille Paquier, Charles Bodet, Jean-François Jégou, Mathilde Pohin, Laure Favot, Martine Garcia, Vincent Huguier, Jiad Mcheik, Corinne Lacombe, Hans Yssel, Gérard Guillet, François-Xavier Bernard, Jean-Claude Lecron
• Journal: PloS one (PLoS One) Vol. 12 Issue 7 Pg. e0181486 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28708859 (Publication Type: Journal Article)

Chemical References

• Aminoquinolines
• Chemokine CCL20
• Cytokines
• Interleukin-17
• Receptors, CCR6
• Recombinant Proteins
• Serum Amyloid A Protein
• Imiquimod

Topics

• Adult
• Aged
• Aminoquinolines (pharmacology)
• Animals
• Cells, Cultured
• Chemokine CCL20 (metabolism, pharmacology)
• Cytokines (genetics, metabolism)
• Dermatitis, Atopic (metabolism, pathology)
• Disease Models, Animal
• Female
• Humans
• Imiquimod
• Interleukin-17 (genetics, metabolism, pharmacology)
• Keratinocytes (cytology, drug effects, metabolism)
• Liver (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Psoriasis (metabolism, pathology)
• Receptors, CCR6 (metabolism)
• Recombinant Proteins (biosynthesis, isolation & purification, pharmacology)
• Serum Amyloid A Protein (analysis, genetics, metabolism)
• Skin (drug effects, metabolism)
• Th17 Cells (cytology, metabolism)
• Up-Regulation (drug effects)