The aim of this study will be investigate the role of adenosine receptors in patients affected by chronic inflammatory disorders correlated with the expression of ectonucleotidases of Treg cells and with specific polymorphism in genes encoding cytokines directly involved in the inflammatory processes associated with rheumatic disorders. The presence of A1, A2A, A2B and A3 adenosine receptors will be evaluated in human lymphocytes from age-matched healthy subjects, RA and SpA patients by using radioligand binding assays, mRNA and western blotting analysis. Adenosine receptor functionality in cAMP production assays, in selected cytokine release (e.g. TNF-alpha, IL-1beta, IL-6 and IL-8) and in the activation of NF-kB will be explored (Unit 1, Pharmacology and Rheumatology Section, Ferrara University, Italy). In addition, the pattern of Treg cells defined by the expression of CD4+, CD25 high, FoxP3+, CD4+IL-17+ will be studied. The expression of ectonucleotidases CD39 and CD73 will be evaluated with the aim to identify a possible involvement of adenosine metabolism in RA and/or SpA (Unit 3 Rheumatology Unit, Padova University, Italy). The genic distribution of polymorphism in genes encoding cytokines directly involved in the inflammatory processes associated with rheumatic disorders will be also studied. In particular, will be investigated the distribution of polymorphism in IL-1beta, IL-Ra, TNF-alpha, TNF-RII and IL-6 genes and their correlation with cytokine expression in the examined patients (Unit 2, Division of Rheumatology, Catholic University, Rome, Italy). These results could indicate the presence of specific polymorphisms associated to some of the most interesting pro-inflammatory cytokines linked to adenosine and adenosine receptors. On the other hand, the ectonucleotidases expression by the T cell subsets will be able to modulate the presence of adenosine and as a consequence the pattern of the pro-inflammatory cytokine expression suggesting a novel link by using adenosine between the genotype and the immunosuppressive mechanisms. In conclusion, the knowledge derived from this research project could suggest individual drug treatments based on the genetic (SNPs), immunological (T cell subsets) and receptor pharmacology (adenosine receptors) characteristics of each patient.

Caratterizzazione farmacologica dei recettori dell'adenosina nel sangue periferico di pazienti affetti da artriti infiammatorie croniche

VARANI, Katia
2011

Abstract

The aim of this study will be investigate the role of adenosine receptors in patients affected by chronic inflammatory disorders correlated with the expression of ectonucleotidases of Treg cells and with specific polymorphism in genes encoding cytokines directly involved in the inflammatory processes associated with rheumatic disorders. The presence of A1, A2A, A2B and A3 adenosine receptors will be evaluated in human lymphocytes from age-matched healthy subjects, RA and SpA patients by using radioligand binding assays, mRNA and western blotting analysis. Adenosine receptor functionality in cAMP production assays, in selected cytokine release (e.g. TNF-alpha, IL-1beta, IL-6 and IL-8) and in the activation of NF-kB will be explored (Unit 1, Pharmacology and Rheumatology Section, Ferrara University, Italy). In addition, the pattern of Treg cells defined by the expression of CD4+, CD25 high, FoxP3+, CD4+IL-17+ will be studied. The expression of ectonucleotidases CD39 and CD73 will be evaluated with the aim to identify a possible involvement of adenosine metabolism in RA and/or SpA (Unit 3 Rheumatology Unit, Padova University, Italy). The genic distribution of polymorphism in genes encoding cytokines directly involved in the inflammatory processes associated with rheumatic disorders will be also studied. In particular, will be investigated the distribution of polymorphism in IL-1beta, IL-Ra, TNF-alpha, TNF-RII and IL-6 genes and their correlation with cytokine expression in the examined patients (Unit 2, Division of Rheumatology, Catholic University, Rome, Italy). These results could indicate the presence of specific polymorphisms associated to some of the most interesting pro-inflammatory cytokines linked to adenosine and adenosine receptors. On the other hand, the ectonucleotidases expression by the T cell subsets will be able to modulate the presence of adenosine and as a consequence the pattern of the pro-inflammatory cytokine expression suggesting a novel link by using adenosine between the genotype and the immunosuppressive mechanisms. In conclusion, the knowledge derived from this research project could suggest individual drug treatments based on the genetic (SNPs), immunological (T cell subsets) and receptor pharmacology (adenosine receptors) characteristics of each patient.
2011
Varani, Katia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1523516
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