We investigated whether or not YopM has the likely to act as being a selfdelivering immune therapeutic agent by minimizing the inflammation and joint destruction linked to RA. Employing confocal laser scanning we analysed the penetration of recombinant YopM into bone marrow macrophages. Additionally we studied the effects of YopM on osteoclastogenesis Torin 2 applying in vitro osteoclast formation assay. To unravel the signaling pathways of YopM, we tested for phosphorylation of MAP kinases and activation of NF KB signaling by Western Blot analysis. With respect to a prospective in vivo application of YopM, we injected YopM intra articular and intravenous in mice and monitored the distribution by fluorescence reflection imaging. We taken care of hTNFtg mice, as animal model for RA, with YopM and recorded clinical parameters.

Eventually we analysed the microtubule phosphorylation destruction of bone and cartilage histologically as compared to untreated hTNFtg mice and wildtype mice. As observed in confocal scanning microscopy, YopM penetrated the cell membrane of BMMs and accumulated near the nucleus. Learning the signaling pathways impacted by YopM, we located that YopM lowered the TNFa induced activation of NF kB by means of reducing the phosphorylation of IkBa. TNFa mediated phosphorylation of MAP kinases have been not altered by YopM. Most interestingly, we identified a strong reduction of osteoclast formation by YopM. Incubation of BMMs with YopM led to a 90% reduction in osteoclasts precursors and osteoclasts. YopM Cy5 injected in to the hind paws of hTNFtg mice was detectable inside the joint with no a systemic distribution for 48 hours and elimination mediated by means of renal clearance.

Analysing the clinical parameters of RA in hTNFtg mice, we observed a delay of onset of paw swelling in mice handled with YopM. At histological examination from the hind paws, we discovered lowered bone destruction and decreased osteoclast formation, too as much less inflammation in YopM taken care of hTNFtg Gene expression mice in comparison to untreated hTNFtg mice. These outcomes propose that YopM has the probable to cut back inflammation and bone destruction in vivo. For that reason YopM may possibly constitute a novel therapeutic agent for your remedy of RA.

P9 PTEN in antigen presenting cells is often a master regulator GSK-3 activation for Th17 mediated autoimmune pathology Stephan Bl?ml1, Gernot Schabbauer2, Eva Hainzl2, Birgit Niederreiter1, Anastasia Hladik1, Tobias Lohmeyer2, Michael Bonelli1, Elisabeth Zinser3, Marije Koenders4, Wim van den Berg4, Giulio Superti Furga5, Josef S Smolen1, Kurt Redlich1 1Division of Rheumatology, Inner Medication III, Healthcare University of Vienna, Austria, 2Institute for Vascular Biology and Thrombosis Study, Center for Biomolecular Medication and Pharmacology, Health care University Vienna, A 1090 Vienna, Austria, 3Department of Dermatology, Hartmannstasse 14, University Hospital Erlangen, 91052 Erlangen, Germany, 4Rheumatology Study and Innovative Therapeutics, Department of Rheumatology, Radboud University Nijmegen Health-related Center, Nijmegen, The Netherlands, 5CeMM Center for Molecular Medicine on the Austrian Academy of Sciences, Vienna 1090, Austria Arthritis Exploration & Therapy 2012, 14 9 Autoreactive T cells are a central element in many systemic autoimmune diseases.