Interleukin‐5 deletion promotes sepsis‐induced M1 macrophage differentiation, deteriorates cardiac dysfunction, and exacerbates cardiac injury via the NF‐κB p65 pathway in mice

Abstract

Inflammation plays a crucial role in sepsis-induced cardiac injury. The purpose of this study was to determine whether interleukin-5 (IL-5) affected lipopolysaccharide (LPS)-induced cardiac injury by regulating the inflammatory response. First, the expression level and source of cardiac IL-5 were examined, and the results showed that LPS treatment and cecal ligation decreased cardiac IL-5 expression in macrophages. In addition, LPS was used to establish a mouse sepsis model, and the effects of IL-5 deletion on cardiac injury, M1 macrophage differentiation and myocardial cell apoptosis were analyzed. The results showed that IL-5 deficiency significantly increased cardiac injury marker expression, worsened cardiac dysfunction, promoted M1 macrophage differentiation and exacerbated myocardial cell apoptosis in LPS-induced septic mice. The nuclear factor-kappa B (NF-κB) p65 pathway was inhibited by JSH-23, and the results showed that treatment with JSH-23 inhibited M1 macrophage differentiation and alleviated cardiac injury in LPS-treated IL-5-knockout mice. Furthermore, the effects of IL-5 deficiency on M1 macrophage differentiation and myocardial cell apoptosis were measured in vitro. The IL-5-mediated promotion of M1 macrophage differentiation was also reversed by S31-201, and the pro-apoptotic effect of IL-5 knockout on macrophage-mediated myocardial cell apoptosis was also reversed by JSH-23. In conclusion, we found that IL-5 knockout may exacerbate sepsis-induced cardiac injury by promoting M1 macrophage differentiation in mice. IL-5 may be a potential target for the clinical prevention of sepsis-related cardiac injury.

Macrophage-Derived Exosomes in TLR9-/- Mice Ameliorate Sepsis-Induced Mitochondrial Oxidative Stress and Apoptosis in Cardiomyocytes

“…In sepsis, proinflammatory cytokines such as TNF- α and IL-1 β trigger the inflammation cascade, inducing a systemic inflammatory cascade response, which can cause myocardial injury, apoptosis, and cardiac dysfunction [ 17 , 40 ]. The protein expressions of cytochrome C, cleaved-Caspase-3, and cleaved-Caspase-9 rose remarkably in the myocardial tissues of septic mice, and they were significantly lower in TLR9 −/− mice than those in WT mice.…”

Vaspin Alleviates Sepsis-Induced Cardiac Injury and Cardiac Inflammation by Inhibiting Kallikrein 7 in Mice

“…Male WT mice and KLK7-/-mice aged 10 weeks were used in this study. First, WT mice were subjected to CLP or stimulated with LPS (10 mg/kg, Sigma) to establish a mouse model of sepsis as described in previous studies [13,14]. Six hours later, vaspin expression was analyzed, while WT mice underwent a sham operation or were administered saline as a control (n = 5 for each group, part 1).…”

“…RPMI 1640 medium (Gibco, USA) with 10% fetal bovine serum was used to culture the cardiomyocytes. First, WT cardiomyocytes were pretreated with PBS or vaspin (80 ng/ml, PeproTech, USA) and then administered saline or LPS (1 μmol/ml, Sigma, USA) [13,20]. Additionally, WT and KLK7-/-cardiomyocytes were pretreated with vaspin or PBS and then stimulated with LPS.…”

Butorphanol alleviates lipopolysaccharide‑induced inflammation and apoptosis of cardiomyocytes via activation of the κ‑opioid receptor

“…1B, LPS significantly reduced the viability of H9C2 cells, whereas butorphanol treatment restored the reduced cell viability induced by LPS in a dose-dependent manner. Inflammation is an important process involved in sepsis-induced cardiac injury (22); thus, the levels of TNF-α, IL-1β and IL-6 were detected. As shown in Fig.…”