Knockout of Toll-like receptor 4 improves survival and cardiac function in a murine model of severe sepsis

Dan Zhou, Yun Zhu, Min‑Zhi Ouyang, Ming Zhang, Kui Tang, Cheng‑Cheng Niu, Ling Li
2018 Molecular Medicine Reports  
Toll-like receptor 4 (TLR4) is a transmembrane pattern-recognition receptor expressed in immune cells and the heart. Activation of TLR4 signaling during sepsis results in the release of cardiac depression mediators that may impair heart function. The present study aimed to determine whether TLR4 contributes to development of severe sepsis-induced myocardial dysfunction. A cecum ligation and puncture (CLP) procedure was employed to establish severe sepsis models. Wild type (WT) and TLR4
more » ... (TLR4-KO) mice were divided into four groups: WT-sham, TLR4-KO-sham, WT-CLP, and TLR4-KO-CLP. Cardiac function of these animals was evaluated at various time points following the surgical procedure. The expression levels of proinflammatory cytokines in the heart tissues were detected by reverse transcription-semi quantitative polymerase chain reaction (RT-PCR). Myocardial neutrophil and macrophage infiltration were investigated by histopathological examination, as well as a myeloperoxidase activity assay in heart tissue by RT-PCR. Myocardium Fas cell surface death receptor/Fas ligand and caspase-3 were also analyzed by RT-PCR. Additionally, myeloid differentiation primary response 88 M, toll or interleukin-1 receptor-domain-containing adapter-inducing interferon-β and nuclear factor-κB expression levels were observed in the myocardium of all four groups. WT-CLP mice exhibited increased mortality rates, more severe cardiac dysfunction and had increased levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α in heart tissues and increased neutrophil infiltration compared with TRL4-KO-CLP mice. The present study reported that TLR4 aggravates severe sepsis-induced cardiac impairment by promoting the release of proinflammatory cytokines and neutrophil infiltration in hearts.
doi:10.3892/mmr.2018.8495 pmid:29393431 fatcat:r4fjwzdpmreszbh5x55eixal2u