Rats on the normal or magnesium-supplemented diets were not protected and developed equally severe and erosive disease. Rats on the low-magnesium diet were significantly and reproducibly protected and had 70% lower median arthritis severity score, with preservation of normal joint histology without erosive changes. Arthritis severity was scored for 38 days, and joints were examined by histology and quantitative PCR for proinflammatory genes. The diets were switched to a normal diet 14 days after the induction of PIA (typical time of disease onset). To examine the effect of dietary magnesium modifications in arthritis severity and joint damage DA rats were placed on one of three diet regimens before the induction of autoimmune pristane-induced arthritis (PIA): a 4 wk low-magnesium diet, normal diet, and a magnesium-supplemented diet. has been suggested to have anti-inflammatory properties in short-term, mostly in vitro studies. KCa1.1 channels regulate β 1-integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes. Together, these data outline a new signaling mechanism by which KCa1.1 regulates β 1integrin function and therefore invasiveness of RA-FLSs.-Tanner, M. Interestingly, the pore-forming α subunit of KCa1.1 coimmunoprecipitates with β 1 integrins, suggesting that this physical association underlies the functional interaction between these molecules. Blocking KCa1.1 disturbs calcium homeostasis, leading to the sustained phosphorylation of Akt and the recruitment of talin to β 1 integrins. Here, we demonstrate that KCa1.1 regulates RA-FLS adhesion through controlling the plasma membrane expression and activation of β 1 integrins, but not α 4, α 5, or α 6 integrins. However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness have remained largely unknown. It is a critical regulator of RA-FLS migration and invasion and therefore represents an attractive target for the therapy of RA. Large-conductance calcium-activated potassium channel (KCa1.1 BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) isolated from the synovium of patients with RA.
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