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

• Published in: PloS one Vol. 12; no. 7; p. e0181486
• Main Authors: Couderc, Elodie, Morel, Franck, Levillain, Pierre, Buffière-Morgado, Amandine, Camus, Magalie, Paquier, Camille, Bodet, Charles, Jégou, Jean-François, Pohin, Mathilde, Favot, Laure, Garcia, Martine, Huguier, Vincent, Mcheik, Jiad, Lacombe, Corinne, Yssel, Hans, Guillet, Gérard, Bernard, François-Xavier, Lecron, Jean-Claude
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.07.2017; Public Library of Science (PLoS)
• Subjects: Acute phase proteins; Acute phase substances; Adaptive immunology; Adult; Aged; Aminoquinolines - pharmacology; Animals; Assaying; Atopic dermatitis; Biochemistry, Molecular Biology; Biology and Life Sciences; CCAAT/enhancer-binding protein; CCL20 protein; CCR6 protein; Cells, Cultured; Chemokine CCL20 - metabolism; Chemokine CCL20 - pharmacology; Cream; Cytokines; Cytokines - genetics; Cytokines - metabolism; Dermatitis; Dermatitis, Atopic - metabolism; Dermatitis, Atopic - pathology; Dermatology; Disease Models, Animal; Enzyme-linked immunosorbent assay; Female; Gene expression; Genetic aspects; Genomics; Glycoproteins; Helper cells; Human health and pathology; Humans; Imiquimod; Immunity; Immunology; Inflammation; Inflammatory diseases; Inflammatory response; Innate immunity; Interleukin; Interleukin 1; Interleukin 22; Interleukin-17; Interleukin-17 - genetics; Interleukin-17 - metabolism; Interleukin-17 - pharmacology; Keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - metabolism; Life Sciences; Ligands; Liver; Liver - drug effects; Liver - metabolism; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; Middle Aged; Mimicry; NF-κB protein; Pathogenesis; Patients; Proteins; Psoriasis; Psoriasis - metabolism; Psoriasis - pathology; Receptors, CCR6 - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Recombinant Proteins - pharmacology; Recruitment; Research and Analysis Methods; Rodents; Serum Amyloid A Protein - analysis; Serum Amyloid A Protein - genetics; Serum Amyloid A Protein - metabolism; Skin; Skin - drug effects; Skin - metabolism; Skin diseases; Stimulation; Synthesis; Th17 Cells - cytology; Th17 Cells - metabolism; Transcription factors; Tumor necrosis factor-TNF; Up-Regulation - drug effects; β-Amyloid; France; expression; differentiation; secretion; oncostatin-m; Protein-coupled receptor; binding; cd36; skin inflammation; kappa-b; rheumatoid-arthritis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181486

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. 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. 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. 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. Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.