Gamma ray-induced bystander effect in tumour glioblastoma cells: a specific study on cell survival, cytokine release and cytokine receptors.

Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.

Designing ionic liquids with boron cluster anions: alkylpyridinium and imidazolium [nido-C(2)B(9)H(11)] and [closo-CB(11)H(12)] carborane salts

A range of new alkylpyridinium and imidazolium carborane salts with [nido-C2B9H12](-), [closo-CB11H12](-), and [RC2B11H11](-) (R = methyl or butyl) anions have been prepared and characterized by physical and thermal methods, including the solid state structures of five of the salts determined by single crystal X-ray diffraction. The tendency of the salts to form low-melting ionic liquids has been assessed; all the salts studied with [nido-C2B9H12](-) anions melted below 100 degrees C and, significantly, have melting points that are 25-85 degrees C lower than those of the corresponding [closo-CB11H12](-) analogs, demonstrating that a wider range of boron-rich ionic liquid materials can be readily accessed.

Documenta 12. Education

Sin resumen

Vegetation and climate c. 12 300-9000 cal. yr BP at Andoya, NW Norway

Owing to proximity of the North Atlantic Stream and the shelf, the And circle divide ya biota are assumed to have responded rapidly to climatic changes taking place after the Weichselian glaciation. Palynological, macrofossil, loss-on-ignition, tephra and C-14 data from three sites at the northern part of the island of And circle divide ya were studied. The period 12 300-11 950 cal. yr BP was characterized by polar desert vegetation, and 11 950-11 050 cal. yr BP by a moisture-demanding predominantly low-arctic Oxyria vegetation. During the period 11 050-10 650 cal. yr BP, there was a climatic amelioration towards a sub-arctic climate and heaths dominated by Empetrum. After 10 650 cal. yr BP the Oxyria vegetation disappeared. As early as about 10 800 cal. yr BP the bryozoan Cristatella mucedo indicated a climate sufficient for Betula woodland. However, tree birch did not establish until 10 420-10 250 cal. yr BP, indicating a time-lag for the formation of Betula ecotypes adapted to the oceanic climate of And circle divide ya. From about 10 150 to 9400 cal. yr BP the summers were dry and warm. There was a change towards moister, though comparatively warm, climatic conditions about 9400 cal. yr BP. The present data are compared with evidence from marine sediments and the deglaciation history in the region. It is suggested that during most of the period 11 500-10 250 cal. yr BP a similar situation as in present southern Greenland existed, with birch woodland in the inner fjords near the ice sheet and low-arctic heath vegetation along the outer coast.

Functional Interleukin-17 Receptor A is Expressed in Central Nervous System Glia and Upregulated in Experimental Autoimmune Encephalomyelitis

Background: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood. Methods: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA. Results: Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA. Conclusion: IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions. © 2009 Sarma et al; licensee BioMed Central Ltd.

Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice

Genetic or vitamin D3-induced overexpression of thymic stromal lymphopoietin (TSLP) by keratinocytes results in an atopic dermatitis (AD)-like inflammatory phenotype in mice echoing the discovery of high TSLP expression in epidermis from AD patients. Although skin dendritic cells (DC) are suspected to be involved in AD, direct evidence of a pathogenetic role for skin DC in TSLP-induced skin inflammation has not yet been demonstrated. In a mouse model of AD, i.e. mice treated with the low-calcemic vitamin D3 analogue, MC903, we show that epidermal Langerhans cells (LC)-depleted mice treated with MC903 do neither develop AD-like inflammation nor increased serum IgE as compared to vitamin D3 analogue-treated control mice. Accordingly, we show that, in mice treated with MC903 or in K14-TSLP transgenic mice, expression of maturation markers by LC is increased whereas maturation of dermal DC is not altered. Moreover, only LC are responsible for the polarization of naive CD4+ T cells to a Th2 phenotype, i.e. decrease in interferon-gamma and increase in interleukin (IL)-13 production by CD4+ T cells. This effect of LC on T-lymphocytes does not require OX40-L/CD134 and is mediated by a concomitant down-regulation of IL-12 and CD70. Although it was previously stated that TSLP up-regulates the production of thymus and activation-regulated chemokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) and macrophage-derived chemokine (MDC)/CCL22 by human LC in vitro, our work shows that production of these Th2- cell attracting chemokines is increased only in keratinocytes in response to TSLP overexpression. These results demonstrate that LC are required for the development of AD in mouse models of AD involving epidermal TSLP overexpression.

Interleukin-4 and interleukin-4 soluble receptor α levels in bronchoalveolar lavage from children with asthma

Background: In asthma there is increased expression of the Th2-type cytokine interleukin-4 (IL-4). IL-4 is important in immunoglobulin isotype switching to immunoglobulin E and adhesion of eosinophils to endothelium.

Objectives: We hypothesized that levels of IL-4 in bronchoalveolar lavage (BAL) fluid would be increased in stable, atopic asthmatic children compared with controls and that levels of its physiologic inhibitor IL-4 soluble receptor α (IL-4sRα) would be correspondingly decreased.

Methods: One hundred sixteen children attending a children's hospital for elective surgery were recruited. A nonbronchoscopic BAL was performed, and IL-4 and IL-4sRα were measured in the BAL supernatants.

Results: There was no significant difference in IL-4 concentrations between atopic asthmatic children, atopic normal controls, and nonatopic normal controls [0.13 pg/mL (0.13 to 0.87) vs 0.13 pg/mL (0.13 to 0.41) vs 0.13 pg/mL (0.13 to 0.5), P = 0.65]. IL-4sRα levels were significantly increased in asthmatic patients compared with atopic controls [6.4 pg/mL (5.0 to 25.5) vs 5.0 pg/mL (5.0 to 9.9), P = 0.018], but not when compared with the nonatopic controls [5.2 pg/mL (5.0 to 10.6), P = 0.19].

Conclusions: Contrary to expectation, IL-4sRα levels are increased in BAL from stable asthmatic children compared with nonatopic controls, and we speculate that IL-4sRα is released by inflammatory cells in the airways to limit the proinflammatory effects of IL-4.