Objective. To investigate A1, A2A, A2B and A3 adenosine receptors in lymphocytes and neutrophils from early rheumatoid arthritis (ERA) patients and after MTX or anti TNF-alpha treatment compared with age-matched healthy controls. To evaluate the correlation between the status and functionality of adenosine receptors, TNF-alpha release and NF-kB activation. Methods. Adenosine receptors were analyzed by saturation binding assays and western blotting analysis. The potency of typical A2A and A3 agonists in cAMP production of control subjects, ERA untreated and treated with MTX or anti TNF-alpha drugs was investigated. In a cohort of RA patients, the TNF-alpharelease and NF-kB activation were evaluated in plasma and in nuclear extracts, respectively. Results. In ERA patients high density and altered functionality of A2A and A3 receptors were present. Binding and functional parameters of A2A and A3 receptors normalized after anti TNF-alpha but not after MTX treatment. TNF-alpha release was increased in ERA and MTX treated patients, whereas in anti TNF-alpha treated patients it was comparable to controls. NF-kB activation was elevated in ERA patients and after MTX treatment. Anti TNF-alpha treatment mediated decreased levels of NF-kB activation. Conclusion. A2A and A3 receptor upregulation in ERA patients and after MTX treatment was associated with high levels of TNF-alpha and NF-kB activation. Anti TNF-alpha treatment normalized A2A and A3 receptor expression and functionality. These new findings, i.e. the evidence of A2A and A3 receptor involvement, open up the possibility of exploiting their potential role in human diseases characterized by a marked inflammatory component.
Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patients by treatment with anti-tumor necrosis factor alpha but not metotrexate
VARANI, Katia;MASSARA, Alfonso;VINCENZI, Fabrizio;TOSI, ALICE;PADOVAN, Melissa;TROTTA, Francesco;BOREA, Pier Andrea
2009
Abstract
Objective. To investigate A1, A2A, A2B and A3 adenosine receptors in lymphocytes and neutrophils from early rheumatoid arthritis (ERA) patients and after MTX or anti TNF-alpha treatment compared with age-matched healthy controls. To evaluate the correlation between the status and functionality of adenosine receptors, TNF-alpha release and NF-kB activation. Methods. Adenosine receptors were analyzed by saturation binding assays and western blotting analysis. The potency of typical A2A and A3 agonists in cAMP production of control subjects, ERA untreated and treated with MTX or anti TNF-alpha drugs was investigated. In a cohort of RA patients, the TNF-alpharelease and NF-kB activation were evaluated in plasma and in nuclear extracts, respectively. Results. In ERA patients high density and altered functionality of A2A and A3 receptors were present. Binding and functional parameters of A2A and A3 receptors normalized after anti TNF-alpha but not after MTX treatment. TNF-alpha release was increased in ERA and MTX treated patients, whereas in anti TNF-alpha treated patients it was comparable to controls. NF-kB activation was elevated in ERA patients and after MTX treatment. Anti TNF-alpha treatment mediated decreased levels of NF-kB activation. Conclusion. A2A and A3 receptor upregulation in ERA patients and after MTX treatment was associated with high levels of TNF-alpha and NF-kB activation. Anti TNF-alpha treatment normalized A2A and A3 receptor expression and functionality. These new findings, i.e. the evidence of A2A and A3 receptor involvement, open up the possibility of exploiting their potential role in human diseases characterized by a marked inflammatory component.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
