Endocrine Abstracts

Acute inflammation plays an important role in the normal immune system by helping to coordinate host responses to danger signals such as infection. In most cases the inflammation is rapidly resolved but in chronic inflammatory diseases such as rheumatoid arthritis (RA) the inflammation persists leading to localized accumulation of potentially damaging immune cells. It remains unclear why inflammation persists in some tissues and not in others. Recent studies have shown that st...

Generalised and periarticular osteoporosis are common features of inflammatory arthritides. These effects appear due to high levels of pro-inflammatory cytokines. 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) is an intracellular enzyme that generates active cortisol from inactive cortisone and is an important determinant of the effects of glucocorticoids on osteoblasts. In vitro, osteoblastic 11b-HSD1 expression is induced by pro-inflammatory cytokines. We thus ...

Fibroblasts are important regulators of local inflammatory responses. These responses are further regulated by tissue glucocorticoid levels. Other stromal lineage cells, adipocytes and osteoblasts, express 11beta-hydroxysteroid dehydrogenases (11b-HSDs) which interconvert inactive cortisone and active cortisol. These enzymes are important regulators of local glucocorticoid levels and their expression is regulated by proinflammatory cytokines. We therefore examined expression o...

We have previously proposed a central role for locally generated glucocorticoids in the periarticular and systemic osteoporosis seen in rheumatoid arthritis (RA). Synovial fibroblasts (SFs) express the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme and this expression increases dramatically with inflammation. Recently, production of DKK-1 (a Wnt signalling inhibitor known to inhibit bone formation) by SFs in response to inflammation has been proposed to ex...