Anti-Toll-like receptor 2 antibody inhibits nuclear factor kappa B activation and attenuates cardiac damage in high-fat-feeding rats.

Long-time consumption of high-fat food is a direct cause of cardiovascular diseases, and high-fat-related inflammation plays an important role in it. Toll-like receptors (TLRs), especially TLR2 and TLR4, play important roles in high-fat-related inflammation. However, the impact of TLR2 on high-fat-associated cardiovascular complications is still unknown. In this study, we try to investigate the relationship between TLR2 and high-fat-related cardiac injury. SD rats were allocated to either a control group which were fed with normal diet or a high-fat group which were fed with high-fat diet for 5 months. At the last month, rats fed with high-fat diet were intraperitoneally injected with control normal mouse IgG or anti-TLR2 antibody. Heart tissues were collected for further analysis. RT-qPCR and western blot analysis results revealed that TLR2 expression was increased in the heart tissues from rats fed with high-fat diet and anti-TLR2 antibody had no effect on TLR2 expression. However, anti-TLR2 antibody alleviated masson staining area, levels of TGF-ß1 and Collagen I mRNA, and decreased TUNEL-positive myocardial cells and caspase-3 activity, suggesting that anti-TLR2 antibody protected cardiac cells against high-fat-induced cardiac fibrosis and cell apoptosis. By using immunohistochemistry, RT-qPCR and ELISA, we found that anti-TLR2 antibody blocked NF-κB activation, inhibited the expression of inflammatory factors such as TNF-α, IL-1ß, IL-6 and IL-18 in the heart tissues from rats fed with high-fat diet. These results hinted that anti-TLR2 antibody might exert its protective effect via inhibition of the TLR2/NF-κB/inflammation pathway. Our findings suggest that anti-TLR2 antibody has a preventive function against high-fat-induced deleterious effects in the heart, and anti-TLR2 antibody may be used as an attractive therapeutic option for high-fat-induced cardiac injury.

DR region specific antibody ameliorated but ouabain worsened renal injury in nephrectomized rats through regulating Na,K-ATPase mediated signaling pathways.

Reduced Na+-K+-ATPase function is reported in various renal diseases. This implies that increase of Na+-K+-ATPase function may be a new target in treatment of renal injury. We previously reported that Na+-K+-ATPase was stabilized by DRm217, a specific antibody against DR region of Na+-K+-ATPase. In this study, we compared the protective effect of DRm217 and ouabain on kidney in a chronic kidney disease rat model and investigated the mechanism under it. We found that DRm217 improved renal function, alleviated glomerulus atrophy, inhibited renal tubular cells apoptosis, tubulointerstitial injury and renal fibrosis in 5/6 nephrectomized rats. Contrary to DRm217, ouabain worsened renal damage. Activated Na+-K+-ATPase /Src signaling pathway, increased oxidant stress and activated inflammasome were responsible for nephrectomized or ouabain-induced renal injury. DRm217 inhibited Na+-K+-ATPase /Src signaling pathway, retarded oxidant stress, suppressed inflammasome activation, and improved renal function, suggesting a novel approach to prevent renal damage.