Interleukin-1β Interferes with Epidermal Homeostasis through Induction of Insulin Resistance: Implications for Psoriasis Pathogenesis

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

Future extreme events in European climate: an exploration of regional climate model projections

This paper presents an overview of changes in the extreme events that are most likely to affect Europe in forthcoming decades. A variety of diagnostic methods are used to determine how heat waves, heavy precipitation, drought, wind storms, and storm surges change between present (1961-90) and future (2071-2100) climate on the basis of regional climate model simulations produced by the PRUDENCE project. A summary of the main results follows. Heat waves - Regional surface warming causes the frequency, intensity and duration of heat waves to increase over Europe. By the end of the twenty first century, countries in central Europe will experience the same number of hot days as are currently experienced in southern Europe. The intensity of extreme temperatures increases more rapidly than the intensity of more moderate temperatures over the continental interior due to increases in temperature variability. Precipitation - Heavy winter precipitation increases in central and northern Europe and decreases in the south; heavy summer precipitation increases in north-eastern Europe and decreases in the south. Mediterranean droughts start earlier in the year and last longer. Winter storms - Extreme wind speeds increase between 45°N and 55°N, except over and south of the Alps, and become more north-westerly than cuurently. These changes are associated with reductions in mean sea-level pressure, leading to more North Sea storms and a corresponding increase in storm surges along coastal regions of Holland, Germany and Denmark, in particular. These results are found to depend to different degrees on model formulation. While the responses of heat waves are robust to model formulation, the magnitudes of changes in precipitation and wind speed are sensitive to the choice of regional model, and the detailed patterns of these changes are sensitive to the choice of the driving global model. In the case of precipitation, variation between models can exceed both internal variability and variability between different emissions scenario

Ilot D Prairie au Duc

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