Lipocalin 2: Novel component of proinflammatory signaling in Alzheimer's disease

Alzheimer's disease (AD) is associated with an altered immune response, resulting in chronic increased inflammatory cytokine production with a prominent role of TNF-α. TNF-α signals are mediated by two receptors: TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). Signaling through TNFR2 is associated with neuroprotection, whereas signaling through TNFR1 is generally proinflammatory and proapoptotic. Here, we have identified a TNF-α-induced proinflammatory agent, lipocalin 2 (Lcn2) via gene array in murine primary cortical neurons. Further investigation showed that Lcn2 protein production and secretion were activated solely upon TNFR1 stimulation when primary murine neurons, astrocytes, and microglia were treated with TNFR1 and TNFR2 agonistic antibodies. Lcn2 was found to be significantly decreased in CSF of human patients with mild cognitive impairment and AD and increased in brain regions associated with AD pathology in human postmortem brain tissue. Mechanistic studies in cultures of primary cortical neurons showed that Lcn2 sensitizes nerve cells to β-amyloid toxicity. Moreover, Lcn2 silences a TNFR2-mediated protective neuronal signaling cascade in neurons, pivotal for TNF-α-mediated neuroprotection. The present study introduces Lcn2 as a molecular actor in neuroinflammation in early clinical stages of AD.—Naudé, P. J. W., Nyakas, C., Eiden, L. E., Ait-Ali, D., van der Heide, R., Engelborghs, S., Luiten, P. G. M., De Deyn, P. P., den Boer, J. A., Eisel, U. L. M. Lipocalin 2: Novel component of proinflammatory signaling in Alzheimer's disease

European ring trial to evaluate ELISAs for the diagnosis of infection with Rift Valley fever virus

A ring trial was organized to evaluate Rift Valley fever virus (RVFV) ELISAs by European laboratories. A total of five ELISAs, two of which specific for IgM antibodies, were evaluated by six participants. Sera were derived from cattle or sheep and originated from either a RVFV endemic area, a RVFV-free area or from experimental infection studies. Cohen's kappa analysis showed higher than 90% agreement of two commercially available ELISAs with the virus neutralization test, suggesting that primary screening as well as serological confirmation using these ELISAs is feasible. More extensive validations with sera of known IgM status are, however, required to determine agreement between IgM ELISAs

Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties.

BACKGROUND: Silica (SiO2) nanoparticles (NPs) are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems. OBJECTIVE: To assess the potential impact of SiO2 NP exposure and NPs chemical modifications in allergic airway inflammation. METHODS: Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 μg) over 42 days, then intratracheally instilled with plain or modified SiO2 NPs (50 μg/mouse), and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue. RESULTS: Plain SiO2 NPs induced proinflammatory and immunomodulatory effects in vivo, highlighted by enhanced infiltration of inflammatory cells in the bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2) cytokine pattern, differentiation of type 2 macrophages, and by morphological changes in the lung of sensitized mice. These effects were dramatically attenuated using surface-functionalized NPs with amino and phosphate groups, but not with polyethylene glycol. The role of macrophages in taking up SiO2 NPs was confirmed by flow cytometry, confocal microscopy, and gene expression analysis. CONCLUSION: Our data suggest that amino and phosphate surface modifications, but not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory effect of SiO2 NPs in allergic airway inflammation, paving the way for new strategies in the production of nanomaterials with lower health impact for humans