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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
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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 effectsCells, CulturedEpidermis/drug effects/immunologyFemaleFumarates/therapeutic useHomeostasis/drug effects/immunologyHumansInsulin Resistance/immunologyInterleukin-1beta/analysis/immunologyKeratinocytes/drug effects/immunology/physiologyMalePsoriasis/drug therapy/immunologyp38 Mitogen-Activated Protein Kinases/metabolism
Identifiers
PMID: 22513786
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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

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Deposited on : 2013-08-12

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