Decreased RAGE expression in peripheral blood mononuclear cells of patients with rheumatoid arthritis.
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%).


CONCLUSIONS
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.
Drinda
S
S
Department of Internal Medicine III, Division of Gastroenterology, Friedrich-Schiller-University, D-07740 Jena, Germany.
Franke
S
S
Eidner
T
T
Schmidt
C
C
Rüster
C
C
Bondeva
T
T
Hein
G
G
Wolf
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D018501:Antirheumatic Agents; D007527:Isoenzymes; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products