Interleukin-1β interferes with epidermal homeostasis through induction of insulin resistance: implications for psoriasis pathogenesis

Buerger, Claudia; Richter, Beatrice; Woth, Kathrin; Salgo, Rebekka; Malisiewicz, Bartosz; Diehl, Sandra; Hardt, Katja; Boehncke, Sandra; Boehncke, Wolf-Henning

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Title		Interleukin-1β interferes with epidermal homeostasis through induction of insulin resistance: implications for psoriasis pathogenesis
Authors		Buerger, Claudia Richter, Beatrice Woth, Kathrin Salgo, Rebekka Malisiewicz, Bartosz Diehl, Sandra Hardt, Katja Boehncke, Sandra Boehncke, Wolf-Henning show all authors [1 - 9]
Published in		Journal of Investigative Dermatology. 2012, vol. 132, no. 9, p. 2206-14
Abstract		Response pathways of the metabolic and the immune system have been evolutionary conserved, resulting in a high degree of integrated regulation. Insulin is a central player in the metabolic system and potentially also in the homeostasis of the skin. Psoriasis is a frequent and often severe autoimmune skin disease, clinically characterized by altered epidermal homeostasis, of which the molecular pathomechanisms are only little understood. In this study, we have examined a potential role for insulin signaling in the pathogenesis of this disease. We show that IL-1β is present in high quantities in tissue fluid collected via microdialysis from patients with psoriasis; these levels are reduced under successful anti-psoriatic therapy. Our results suggest that IL-1β contributes to the disease by dual effects. First, it induces insulin resistance through p38MAPK (mitogen-activated protein kinase), which blocks insulin-dependent differentiation of keratinocytes, and at the same time IL-1β drives proliferation of keratinocytes, both being hallmarks of psoriasis. Taken together, our findings point toward insulin resistance as a contributing mechanism to the development of psoriasis; this not only drives cardiovascular comorbidities, but also its cutaneous phenotype. Key cytokines inducing insulin resistance in keratinocytes and kinases mediating their effects may represent attractive targets for novel anti-psoriatic therapies.
Keywords		Cell Proliferation/drug effects — Cells, Cultured — Epidermis/drug effects/immunology — Female — Fumarates/therapeutic use — Homeostasis/drug effects/immunology — Humans — Insulin Resistance/immunology — Interleukin-1beta/analysis/immunology — Keratinocytes/drug effects/immunology/physiology — Male — Psoriasis/drug therapy/immunology — p38 Mitogen-Activated Protein Kinases/metabolism
Identifiers		DOI: 10.1038/jid.2012.123 PMID: 22513786
Full text		Article (Published version) (2.5 MB) - Limited access to UNIGE
Citation (ISO format)		BUERGER, Claudia et al. Interleukin-1β interferes with epidermal homeostasis through induction of insulin resistance: implications for psoriasis pathogenesis. In: Journal of Investigative Dermatology, 2012, vol. 132, n° 9, p. 2206-14. https://archive-ouverte.unige.ch/unige:29220