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

Abstract

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-β1 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-1β, 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.

Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats

“…They play a significant role in myocardial inflammation as they activate the expression of several pro-inflammatory cytokine genes ( Vaure and Liu, 2014 ). They are bound to the MyD88 (adapter molecule), on activating NF-κB ( Wang et al, 2019b , Yang et al, 2016 ).…”

NOX1 promotes myocardial fibrosis and cardiac dysfunction via activating the TLR2/NF-κB pathway in diabetic cardiomyopathy

“…Previous research has confirmed this ( Peterson et al, 2018 ). Wang W. Z. et al (2019b )found that anti-TLR2 antibody inhibits NF-κB activation and reduces cardiac damage in high-fat-feeding rats. Our study also confirmed that TLR2 regulated the activation of NF-κB.…”

The virulence factor GroEL directs the osteogenic and adipogenic differentiation of human periodontal ligament stem cells through the involvement of JNK/MAPK and NF‐κB signaling

“…Previous studies have demonstrated that after stimulation, the intracellular signaling cascade causes the release of NF-κB dimer, and NF-κB dimer is further activated by various post-translational modifications and transferred to the nucleus, where it binds to the target gene and become acetylated to initiate the transcription of the target gene. 35,36 It is known that JNK/SAPKs are associated with metabolism, motility, apoptosis and proliferation; when stimulated, some activated JNK transfers into the nucleus to regulate a variety of transcription factors, such as c-Jun, activator protein 1 (AP-1) and p53. 37 In this study, the IF staining results showed that GroEL treatment accelerated the nuclear accumulation of p-JNK and total NF-κB in hPDLSCs, and the level of acetylated NF-κB in the nucleus increased.…”