Alessandra Facchi

Interleukin-1β Released by gp120 Drives Neural Death through Tyrosine Phosphorylation and Trafficking of NMDA Receptors

Interleukin-1β is a proinflammatory cytokine implicated under pathological conditions involving NMDA receptor activation, including the AIDS dementia complex (HAD). No information is available on the molecular mechanisms recruited by native interleukin-1β produced under this type of condition. Using a sandwich co-culture of primary hippocampal neurons and glia, we investigated whether native interleukin-1β released by HIV-gp120-activated glia (i) affects NMDAR functions and (ii) the relevance on neuronal spine density and survival, two specific traits of HAD. Increased phosphorylation of NR2B Tyr-1472 was observed after 24 h of exposure of neurons to 600 pm gp120. This effect occurred only when neurons were treated in the presence of glial cells and was abolished by the interleukin-1 receptor antagonist (IL-1ra). Gp120-induced phosphorylation of NR2B resulted in a sustained elevation of intracellular Ca2+ in neurons and in a significant increase of NR2B binding to PSD95. Increased intracellular Ca2+ was prevented by 10 μm ifenprodil, that selectively inhibits receptors containing the NR2B, by interleukin-1ra and by Ca-pYEEIE, a Src family SH2 inhibitor peptide. These last two inhibitors, prevented also NR2B binding to PSD95. Finally, gp120 reduced by 35% of the total PSD95 positive spine density after 48 h of treatment and induced by 30% of the neuronal death. Again, both of these effects were blocked by Ca-pYEEIE. Altogether, our data show that gp120 releasing interleukin-1β from glia increases tyrosine phosphorylation of NMDAR. Thus, tyrosine phosphorylation may contribute to the sensitization of the receptor increasing its function and synaptic localization. Both of these effects are relevant for neurodegeneration.

Enterodiol and Enterolactone Modulate the Immune Response by Acting on Nuclear Factor-κB (NF-κB) Signaling

Lignan-rich whole-grain cereals, beans, berries, and nuts show protective effects against a variety of chronic diseases, including cancer. Lignans are converted by intestinal microflora to enterolactone (EL) and its oxidation product enterodiol (ED). To investigate the immunomodulatory effect of EL and ED in human cells, peripheral blood lymphocytes were treated with increasing physiologically relevant concentrations of EL and ED (0-1000 microM) and stimulated with lipopolysaccharide (LPS) and anti-CD3 plus anti-CD28 monoclonal antibodies. A dose-related inhibition of cell proliferation and cytokine production was observed, with EL being the most active. Molecular investigations in THP-1 cells showed that both EL and ED prevented inhibitory-kappaB (I-kappaB) degradation and nuclear factor-kappaB (NF-kappaB) activation, which in turn resulted in decreased tumor necrosis factor-alpha (TNF-alpha) production. EL and ED were also able to pass the intestinal barrier and modulate cytokine production. The findings of the present study reveal potential mechanisms that could explain some in vivo beneficial effects of lignans.

Pratica dei diritti umani e pluralismo giuridico nella ricerca antropologica

Starting from different notions of human rights practice and from the anthropological debate on human rights, the author considers two different models of relationship between Human Rights and Legal pluralism. On the basis of some anthropological researches concerning the processes of localization of rights, she finally points out the existence of limits in these processes and the necessity to maintain a correspondence between human rights practice and the principles of human rights law and theory.

Forme di giustizia e forme di verità: presentazione

One of the fundamental functions fulfilled by law in the course of legal proceedings is that of ascertaining a certain truth, although it may not be the truth, sole and absolute. In so doing, law caters for a widespread social need for truth. The dossier contains an edited version of the presentations made at the conference entitled Justice and Truth: A reconnaissance of the function of truth, held in Milan on 27 February 2012, which sheds light from a variety of perspectives on the relationship between law, legal proceedings and truth.

Multicultural Policies and Female Immigration in Europe

In this paper the author focuses on some of the topics in the debate on multiculturalism, applying them to the issue of immigration, particularly female immigration, in Europe. She then illustrates how the individual/group relationship is a particularly complex one where women are concerned. In this framework she considers the various roles of a multicultural law and the thorny relation between women immigrants and their official representatives. She concludes by asserting the need to place individual rights before group rights and to ensure that women obtain autonomous access to both sets of rights.