These results were confirmed both in primary mouse HSCs and in a human HSC cell line (LX-2). Noteworthy, MG-132 mw TNF-α appeared to be involved in the induction of the tissue inhibitor of metalloproteinase-1 only in a murine model. The authors attempted to explain this discrepancy, forgetting to highlight the fact that mouse HSC are primary, whereas LX-2 are immortalized, cells. Moreover, the lack of TNFR1 inhibited HSC proliferation only upon platelet-derived growth factor (PDGF) stimulation. The authors suggested that this effect might be mediated by PI3K/AKT signaling impairment, as well as by a direct/indirect crosstalk between

TNF and PDGF receptors. It is reasonable that nuclear factor kappaB (NF-κB) upstream and downstream

molecules are potential mediators of suppressed PDGF-dependent proliferation, due to the absence of functioning of TNFR1. Although these NF-κB-associated mediators still remain obscure, we believe that protein kinase R (PKR) could be a potential candidate. It is well known that PKR is critical to cell proliferation. Specifically, it has been demonstrated that TNF-induced cell proliferation is suppressed in PKR-deficient cells.2 In addition, PKR has been described as being involved in PDGF signaling, although its specific PKC inhibitor role has still not been elucidated.3 Taken together, these data suggest that PKR is a possible mediator at the interface in the suggested crosstalk between PDGF and TNF receptor

signaling. We analyzed the expression and/or activation of PKR in LX-2 cells treated with TNF-α (10 ng/mL) at different timepoints. As shown in Fig. 1A, TNF-α stimulation resulted in a statistically significant increase of HSC proliferation at 24 hours. Moreover, western blot analysis showed an up-regulation of PKR protein selleck chemical expression in TNF-α-treated cells at 48 hours and 96 hours (Fig. 1B). Altogether, these results support our hypothesis that PKR might be the critical molecular link between PDGF and TNFR1 signaling pathways. The role of PKR in regulating PDGF-mediated HSC proliferation and activation, and its correlation with TNFR1, require further studies. However, the findings from the study by Tarrats et al., together with our results, add novel interesting perspectives for designing targeted molecular approaches against liver fibrogenesis. Sara Ceccarelli XX*, Nadia Panera XX*, Anna Alisi XX*, Valerio Nobili XX*, * Liver Research Unit, Bambino Gesù Children’s Hospital and Research Institute, Rome, Italy. “
“Host cytoskeletal proteins of the ezrin-moesin-radixin (EMR) family have been shown to modulate single-stranded RNA virus infection through regulating stable microtubule formation. Antibody engagement of CD81, a key receptor for hepatitis C virus (HCV) entry, induces ezrin phosphorylation.