Scientific article

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

Published inJournal of investigative dermatology, vol. 132, no. 9, p. 2206-2214
Publication date2012

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.

  • 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
Affiliation Not a UNIGE publication
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. 2206–2214. doi: 10.1038/jid.2012.123
Main files (1)
Article (Published version)
ISSN of the journal0022-202X

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