title: Interleukin-1β interferes with epidermal homeostasis through induction of insulin resistance: implications for psoriasis pathogenesis.
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.
authors.affiliation: Department of Dermatology, Clinic of Goethe University, Frankfurt am Main, Germany. Claudia.Buerger@kgu.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Buerger
authors.forename: Beatrice
authors.initials: B
authors.lastname: Richter
authors.forename: Kathrin
authors.initials: K
authors.lastname: Woth
authors.forename: Rebekka
authors.initials: R
authors.lastname: Salgo
authors.forename: Bartosz
authors.initials: B
authors.lastname: Malisiewicz
authors.forename: Sandra
authors.initials: S
authors.lastname: Diehl
authors.forename: Katja
authors.initials: K
authors.lastname: Hardt
authors.forename: Sandra
authors.initials: S
authors.lastname: Boehncke
authors.forename: Wolf-Henning
authors.initials: WH
authors.lastname: Boehncke
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004817:Epidermis / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005650:Fumarates / Q000627:therapeutic use; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology*; D053583:Interleukin-1beta / Q000032:analysis / Q000276:immunology*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008297:Male; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005650:Fumarates; C508585:IL1B protein, human; D053583:Interleukin-1beta; D048051:p38 Mitogen-Activated Protein Kinases