OBJECTIVE: Interactions between the multiligand receptor for advanced glycation end products (RAGE) and its proinflammatory ligands (AGEs, S100/calgranulins, HMBG1, Mac-1) may contribute to inflammatory responses playing a key role in the pathogenesis of chronic inflammatory diseases such as in rheumatoid arthritis (RA). Peripheral blood mononuclear cells (PBMCs) participate in the development of chronic inflammatory diseases. This study investigated expression of the RAGE variants endogenous secretory RAGE (esRAGE), N-truncated RAGE (NtRAGE) and complete RAGE (cRAGE: encoding full-length RAGE, esRAGE and NtRAGE) in PBMCs of patients with RA in comparison to healthy control subjects (controls) and to patients with Crohn's disease (CD) as another chronic inflammatory disease. METHODS: The cRAGE, esRAGE and NtRAGE mRNA expression levels of PBMCs from controls, RA and CD patients were measured by real-time PCR. The RAGE protein expression was determined by Western blot analysis and the esRAGE plasma levels by ELISA. RESULTS: PBMCs of RA patients showed significantly decreased mRNA expression for cRAGE (46%), esRAGE (54.0%) and NtRAGE (52%) in comparison to healthy controls (100%). For CD patients, also a down-regulation but to a lower extent was found (cRAGE: 79%; esRAGE: 76%; NtRAGE: 69%). Related to controls, RA PBMCs showed a significantly reduced protein expression of full-length RAGE (53%) as well as significantly decreased esRAGE plasma concentrations (70%). CONCLUSION: The down-regulation of RAGE isoforms in RA PBMCs may contribute to reduced intracellular responses mediated by the cell-standing receptor as well as to a lowered capability of trapping inflammatory ligands by circulating esRAGE.
OBJECTIVE: Interactions between the multiligand receptor for advanced glycation end products (RAGE) and its proinflammatory ligands (AGEs, S100/calgranulins, HMBG1, Mac-1) may contribute to inflammatory responses playing a key role in the pathogenesis of chronic inflammatory diseases such as in rheumatoid arthritis (RA). Peripheral blood mononuclear cells (PBMCs) participate in the development of chronic inflammatory diseases. This study investigated expression of the RAGE variants endogenous secretory RAGE (esRAGE), N-truncated RAGE (NtRAGE) and complete RAGE (cRAGE: encoding full-length RAGE, esRAGE and NtRAGE) in PBMCs of patients with RA in comparison to healthy control subjects (controls) and to patients with Crohn's disease (CD) as another chronic inflammatory disease. METHODS: The cRAGE, esRAGE and NtRAGE mRNA expression levels of PBMCs from controls, RA and CDpatients were measured by real-time PCR. The RAGE protein expression was determined by Western blot analysis and the esRAGE plasma levels by ELISA. RESULTS: PBMCs of RApatients showed significantly decreased mRNA expression for cRAGE (46%), esRAGE (54.0%) and NtRAGE (52%) in comparison to healthy controls (100%). For CDpatients, also a down-regulation but to a lower extent was found (cRAGE: 79%; esRAGE: 76%; NtRAGE: 69%). Related to controls, RA PBMCs showed a significantly reduced protein expression of full-length RAGE (53%) as well as significantly decreased esRAGE plasma concentrations (70%). CONCLUSION: The down-regulation of RAGE isoforms in RA PBMCs may contribute to reduced intracellular responses mediated by the cell-standing receptor as well as to a lowered capability of trapping inflammatory ligands by circulating esRAGE.