Mette Birch Kristensen

Distribution of interleukin 1 receptor antagonist protein (IRAP), interleukin 1 receptor, and interleukin 1α in normal and psoriatic skin. Decreased expression of IRAP in psoriatic lesional epidermis

Summary The distribution of interleukin 1α (IL‐1α), type 1 interleukin 1 receptor (IL‐1R), and the interleukin 1 receptor antagonist protein (IRAP), was investigated in biopsies of normal skin, and in uninvolved and lesional skin of patients with psoriasis, using specific monoclonal antibodies. We report the novel finding that IRAP is distributed throughout the living layers of the epidermis in normal skin, and is also associated with sebaceous glands and eccrine sweat glands. Our finding that the inhibitor protein IRAP is present in areas where the pro‐inflammatory cytokine IL‐1α is distributed provides strong evidence in favour of a cytokine regulatory system in normal skin. We further document for the first time that IL‐1R in normal skin is localized to the living layers of the epidermis, sebaceous and eccrine glands, as well as to a prominent network of dermal dendritic cells, and upper dermal blood vessels. There was a consistent reduction in the level of IRAP expression in lesional compared with uninvolved skin in biopsies from six out of seven psoriasis patients. Decreased IRAP expression in lesions of psoriasis indicates that alterations in the level of this inhibitor protein may be important in the pathogenesis of inflammatory skin conditions.

1,25(OH)2-D3 is a potent regulator of interleukin-1 induced interleukin-8 expression and production.

Interleukin 8 (IL-8) is a potent leukocyte chemotactic and activating cytokine produced by keratinocytes, fibroblasts, peripheral blood monocytes (PBMC) and endothelial cells. IL-8 is believed to play an important role in the development of inflammation and is thus an obvious target for therapeutical modulation. We studied the possible effect of an endogenous immune modulator 1,25(OH)2-cholecalciferol (1,25(OH)2-D3) on the IL-1-induced IL-8-production by several types of cells. 1,25(OH)2-D3 inhibited the IL-1-alpha induced IL-8 production and mRNA expression in keratinocytes, fibroblasts and PBMC, but not in endothelial cells. Optimal vitamin concentrations varied between 10(-10) and 10(-11) M. These results suggest a potential role of this hormone in the regulation of chemotactic cytokine production.

Increased tryptase levels in suction-blister fluid from patients with urticaria.

The levels of tryptase in the suction‐blister fluid from patients with chronic urticaria, urticaria pigmentosa, cholinergic urticaria, urticarial dermographism, prurigo of unknown origin, eczema, psoriasis, atopic dermatitis, and from healthy controls were studied. The blister fluid from controls contained up to 15 μg/l of tryptase, whereas that from patients with active urticaria contained > 50 μg/l. This study demonstrates that patients with urticaria have mast cells that readily release tryptase in both the lesional and non‐lesional areas of skin.

ETH615, a synthetic inhibitor of leukotriene biosynthesis and function, also inhibits the production of and biological responses towards interleukin-8

Abstract ETH6I5 (4‐(2‐quinolylmethoxy)‐N‐(3‐fluorobenzyl‐phenyl‐amino‐methyl‐4‐benzoic‐acid), a synthetic inhibitor of leukotriene B4 production and activities, was tested for its effect on the production of and biological responses towards human interleukin‐8. We found that ETH615 inhibits lipopolysaccharide‐induced (LPS‐induced) expression of interleukin‐8 messenger‐RNA (mRNA) and interleukin‐8 production in human peripheral blood mononuclear cells. We also observed that ETH615 completely inhibited interleukin‐8 as well as leukotriene B4 directed chemotaxis of human neutrophils in a dose‐dependent manner. A moderate effect on fMLP‐directed neutrophil chemotaxis was observed. Further, no significant effect on either interleukin‐8. leukotriene B4 or fMLP‐directed T‐cell migration was observed. These results further support the concept of a cytokine‐leukotriene regulatory circuit and encourage the establishment of clinical trials testing the effect of ETH615 on inflammatory skin diseases, which are characterized by high levels of interleukin‐8 and leukotriene B4 in lesional skin.

Counter-ion Transport Number and Membrane Potential in Working Membrane Systems

In this work we use the general space-charge (SC) theory for a combined transport model of fluid and ion through cylindrical nanopores to derive equations for the membrane potential and counter-ion transport numbers. We discuss this approach for ion exchange membranes assuming aqueous domains as interconnected network of cylindrical pores. The transport number calculations from the SC theory are compared with the corresponding ones from the uniform potential (UP) and Teorell-Meyer-Sievers (TMS) models in the case of both zero and non-zero concentration gradient across the membrane and with an applied current density. By using this approach we suggest the optimal conditions for performing membrane potential experiments (i.e. choice of electrolyte and concentration difference) depending on an easily accessible membrane property, namely the volumetric charge density. We also theoretically describe a novel dynamic method to determine in a single experiment the membrane potential and membrane conductivity. To exemplify the use of the dynamic method we report the calculations based on typical operating conditions of the reverse electrodialysis process. The numerical results are presented in terms of the electrical potential difference versus the average pore radius and charge density. The resulting map is a useful tool for a rational design of an effective membrane morphology for a specific electrochemical application.

Data on flow cell optimization for membrane-based electrokinetic energy conversion

This article elaborates on the design and optimization of a specialized flow cell for the measurement of direct conversion of pressure into electrical energy (Electrokinetic Energy Conversion, EKEC) which has been presented in Østedgaard-Munck et al. (2017) [1]. Two main flow cell parameters have been monitored and optimized: A) the hydraulic pressure profile on each side of the membrane introduced by pumps recirculating the electrolyte solution through the flow fields and B) the electrical resistance between the current collectors across the combined flow cell. The latter parameter has been measured using four-point Electrochemical Impedance spectroscopy (EIS) for different flow rates and concentrations. The total cell resistance consists of contributions from different components: the membrane (Rmem), anode charge transfer (RA), cathode charge transfer (RC), and ion diffusion in the porous electrodes (RD). The intrinsic membrane properties of Nafion 117 has been investigated experimentally in LiI/I2 solutions with concentrations ranging between 0.06 and 0.96 M and used to identify the preferred LiI/I2 solution concentration. This was achieved by measuring the solution uptake, internal solution concentration and ion exchange capacity. The membrane properties were further used to calculate the transport coefficients and electrokinetic Figure of merit in terms of the Uniform potential and Space charge models. Special attention has been put on the streaming potential coefficient which is an intrinsic property.