Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis

Abstract

MRP8 and MRP14 are specifically released during the interaction of monocytes with inflammatory activated endothelium, probably at sites of local inflammation. Their serum concentrations represent a useful marker for monitoring local inflammation in JRA.

Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations

“…Two other S100 proteins, S100A8 and S100A9, were also found in high concentrations in patients with JRA, especially in those with therapy-refractory systemic-onset JRA (49)(50)(51). These proteins are more abundant and are not restricted to granulocytes, where they contribute to ϳ50% of the cytosolic protein.…”

RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response

“…Incubation of mock-transfected CHO cells with a physiologically-relevant concentration of EN-RAGE, 4 10 g/ml, did not significantly increase intensity of the bands corresponding to phosphorylated MEK 1/2 or p44/42 MAP kinases [22][23] (Figure 4d,e, respectively; lanes 1-5). However, exposure of RAGE 82G CHO transfectants to EN-RAGE increased by 2.2-fold and 1.9-fold phosphorylated MEK 1/2 and p44/42 MAP kinases, compared with cultures incubated with BSA alone (P Ͻ 0.01; Figure 4d,e respectively; lanes 7 and 6).…”

“…1 S100/calgranulins, proinflammatory signal transduction ligands of the receptor, are enriched in joints of subjects with rheumatoid arthritis (RA). [2][3][4] Members of this family of molecules, long-associated with classic immune/ inflammatory disorders, 5,6 may be released by activated inflammatory effector cells such as monocytes, 7 thereby freeing them to engage cell surface RAGE and amplify host inflammatory responses. Indeed, accumulation of S100/calgranulins in synovial fluid and plasma of subjects with RA has been correlated with indices of disease severity, such as bony erosions.…”

“…Indeed, accumulation of S100/calgranulins in synovial fluid and plasma of subjects with RA has been correlated with indices of disease severity, such as bony erosions. 4 Recent studies have highlighted the possibility that polymorphisms within key domains of RAGE may influence its function, so that under conditions of increased ligand accumulation, individuals may be predisposed to heightened inflammatory responses. 8,9 Importantly, a polymorphism of the RAGE gene has been identified within the V-type immunoglobulin domain in the extracellular region of the receptor, consisting of a glycine to serine change at position 82.…”

How RAGE turns in rage

“…The observation that the levels of MRP8 and 14 were elevated in juvenile RA and correlated with disease activity is in support for a role of EN-RAGEs in chronic inflammation. 11 It is in this context that the authors performed studies in a collagen-induced murine arthritis model, which demonstrated that blockade of RAGE suppressed clinical, molecular and histological evidence of arthritis, thereby supporting a functional role for RAGE in arthritis. 4 These findings made the RAGE gene an attractive candidate to study for the existence of allelic variations that might be important in the pathogenesis of inflammatory disease.…”