| Grant number: | 12/07784-4 |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| Start date: | August 01, 2012 |
| End date: | July 31, 2013 |
| Field of knowledge: | Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology |
| Principal Investigator: | Maria Christina Werneck de Avellar |
| Grantee: | Alexandre Denadai Souza |
| Supervisor: | Nathalie Vergnolle |
| Host Institution: | Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
| Institution abroad: | Université Paul Sabatier - Toulouse III, France |
| Associated to the scholarship: | 09/12375-3 - Role of the protein SPAG11 in the modulation of experimental arthritis, BP.PD |
Abstract The gene of human sperm-associated antigen 11 (hSPAG11) is localized within a ²-defensin cluster in the chromosome 8p23. Alternative splicing mechanism involving the differential recruitment of 2 promoters and multiple exons results in 7 distinct transcripts in humans (hSPAG11A, B, C, D, E, G and H). While a role for SPAG11 in innate host defence and reproduction has emerged, the mechanism of action is unknown. Otherwise, a recent in vitro study characterized hSPAG11D and its N-terminal domain (shared with the isoform hSPAG11C), as potent inhibitors of the serino-proteinase tryptase, an important mediator of inflammation that activates Proteinase-Activated Receptor 2 (PAR2). The aim of the present study is to investigate whether the heterologous expression of hSPAG11C and D modulates the development of experimental arthritis by inhibiting the pro-inflammatory pathway tryptase/PAR2. Over-expression of recombinant hSPAG11 isoforms in the mouse knee joint will be achieved by an intra-articular transduction of lentiviral particles in association with Vpx-VLPs, where the genes encoding to hSPAG11 isoforms were inserted by directional cloning. Male wild-type or F2rl1 (PAR2) knockout C57BL/6 mice over-expressing recombinant hSPAG11C, D or E (the former as control) will be submitted to mBSA/IL-1²-induced arthritis. After all, several inflammatory parameters will be analysed, such as oedema formation, histopathology, myeloperoxidase and serino-protease activities and the pattern of cytokines Th1/2 and 17. (AU) | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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