Glucocorticoid metabolism in rheumatoid arthritis

Abstract

Endogenous glucocorticoids are implicated in the development and resolution of inflammation. Until recently it was thought that these glucocorticoids arose primarily from the adrenal gland. However, it is now known that several cell types can generate active glucocorticoids within their cytoplasm through expression of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. In a more limited range of cell types, glucocorticoids can be inactivated by the related 11β-HSD2 enzyme. Both enzymes are regulated by inflammation in various settings. In rheumatoid arthritis, 11β-HSD activity is present in the inflamed synovium and appears to influence articular and extraarticular disease processes. The generation of active glucocorticoids in the synovium is strongly linked to the level of inflammation. This local production of glucocorticoids is likely to have paracrine consequences and could underpin inflammation-associated bone loss. The role of 11β-HSD enzymes in the severity and persistence of inflammatory arthritis in a clinical setting is currently being explored.

Increased Expression of 11<i>β</i>-Hydroxysteroid Dehydrogenase Type 1 in Experimental Periodontitis Induced by Lipopolysaccharide from <i>Porphyromonas gingivalis</i>

“…As expected, the expression of 11β-HSD1 was increased in chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel diseases [16] [17] [18] [19]. We recently reported that the expression of 11β-HSD1 was increased in gingival tissues of patients with another chronic inflammatory disease, chronic periodontitis [20].…”

Anti-Inflammatory, Anti-Osteoclastogenic and Antioxidant Effects of Malva sylvestris Extract and Fractions: In Vitro and In Vivo Studies

“…Multipronged therapeutic approaches are needed to treat chronic inflammatory diseases, and the most potent drug interventions may increase the risk of adverse effects [ 28 ]. Glucocorticoids are commonly used as a reference drug when treating chronic inflammation, and their major adverse effect is additional bone loss [ 29 ].…”

DNMT1 activates the canonical Wnt signaling in rheumatoid arthritis model rats via a crucial functional crosstalk between miR-152 and the DNMT1, MeCP2

“…Rheumatoid arthritis (RA) is a chronic, systematic and autoimmune disease that can severely affect synovial membranes and multiple joint structures [1,2]. In some cases, it also can be associated with extraarticular manifestations, mainly involving heart, lung and renal functions [3].…”