Scientific Article
previous document  unige:29220  next document
add to browser collection

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
show hidden authors 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 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
PMID: 22513786
Full text
Article (Published version) (2.5 MB) - document accessible for UNIGE members only Limited access to UNIGE
(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. doi: 10.1038/jid.2012.123

433 hits

0 download


Deposited on : 2013-08-12

Export document
Format :
Citation style :