TRPA1 expression is downregulated by dexamethasone and aurothiomalate in human chondrocytes: TRPA1 as a novel factor and drug target in arthritis

Abstract

Transient receptor potential ankyrin 1 (TRPA1) is a ligand-gated membrane-bound cation channel. TRPA1 has been largely studied in neurons, where it mediates pain and neurogenic inflammation and acts as a chemosensor for harmful exogenous compounds. 1 2 More recently, TRPA1 has been found to be activated also by endoge-nous compounds formed in inflammatory conditions characteristic to arthritis, such as reactive oxygen and nitrogen species. 3 We have recently discovered that TRPA1 is functionally expressed in primary human osteoarthritic chondrocytes, 4 where it upregulated the production of mediators related to arthritis: interleukin (IL)-6, pros-taglandin E 2 and matrix metalloproteinases 1, 3 and 13. 4 Furthermore, we showed in monosodium iodoacetate-induced experi-mental arthritis that TRPA1 activation medi-ates inflammation, cartilage degradation and pain. 5 TRPA1 thus emerges as a novel factor associated with arthritis. Therefore, we investigated the effects of disease-mod-ifying antirheumatic drugs methotrexate, sulfasalazine, hydroxychloroquine and aurothiomalate, glucocorticoid dexameth-asone and non-steroidal anti-inflammatory drug ibuprofen on the expression of TRPA1 in human chondrocytes. Human T/C28a2 chondrocytes 6