New Treatment for psoriasis: therapeutic efficiency in patients and antiinflammatory effect in vitro

Background: Psoriasis is a worldwide chronic inflammatory disease that is increasingly being considered as a systemic disorder. Antioxidant and anti-inflammatory molecules have been revealed as potential adjuvants for traditional therapies.Objectives: To evaluate the antiinflammatory action of selected antioxidant molecules and their beneficial effect as combination therapy in psoriatic patients. Materials & Methods: Thirty-five patients with mild (five), moderate (nine) and severe (twenty one) psoriasis were selected and treated with EP2311454 treatment. PASI, BSA and DLQI assessed the severity of psoriasis and the impact on quality of life. The antiinflammatory effect was tested in IFN-γ stimulated Raw264.7 macrophages that express human PPARG.Results: The combined use in vitro of several EP2311454 components exerts a synergistic inhibitory effect on the expression of the proinflammatory mediators Cox2, Nos2 and Cxcl9. Clinically, more than 80% reduction in DLQI levels is observed after treatment, and 100% of severe patients achieved PASI 75 and significant reduction of BSA levels after 15 days of treatment.Conclusion: EP2311454 treatment, composed by antioxidant molecules, proved to be antiinflammatory in vitro and showed efficacy in patients with mild to severe psoriasis, as demonstrated by a significant decrease in PASI, BSA and DLQI levels

Induction of CIITA by IFN-γ in macrophages involves STAT1 activation byJAK and JNK

The induction of major histocompatibility complex (MHC) class II proteins by interferon gamma (IFN-γ) in macrophages play an important role during immune responses. Here we explore the signaling pathways involved in the induction by IFN-γ of the MHC II transactivator (CIIta) required for MHC II transcriptional activation. Cyclophilin A (CypA) is required for IFN-γ-dependent induction of MHC II in macrophages, but not when it is mediated by GM-CSF. The effect of CypA appears to be specific because it does not affect the expression of other molecules or genes triggered by IFN-γ, such as FcγR, NOS2, Lmp2, and Tap1. We found that CypA inhibition blocked the IFN-γ-induced expression of CIIta at the transcriptional level in two phases. In an early phase, during the first 2 h of IFN-γ treatment, STAT1 is phosphorylated at Tyrosine 701 and Serine 727, residues required for the induction of the transcription factor IRF1. In a later phase, STAT1 phosphorylation and JNK activation are required to trigger CIIta expression. CypA is needed for STAT1 phosphorylation in this last phase and to bind the CIIta promoter. Our findings demonstrate that STAT1 is required in a two-step induction of CIIta, once again highlighting the significance of cross talk between signaling pathways in macrophages

Peptides conjugated to gold nanoparticles induce macrophage activation

Macrophages that react against pathogenic organisms can also be activated with artificial nanometric units consisting of gold nanoparticles (Au NPs) with a peptide coating. Using bone marrow-derived macrophages, here we show that these cells have the capacity to recognize Au NPs once conjugated to two biomedically relevant peptides, the amyloid growth inhibitory peptide (AGIP) and the sweet arrow peptide (SAP), while they do not recognize peptides or NPs alone. The recognition of these conjugates by macrophages is mediated by a pattern recognition receptor, the TLR-4. Consequently, pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, as well as nitric oxide synthase were induced and macrophage proliferation was stopped when exposed to the peptide-conjugated Au NPs. Contamination by lipopolysaccharide in our experimental system was excluded. Furthermore, macrophage activation appeared to be independent of peptide length and polarity. As a result of macrophage activation, conjugate