Interleukin-9 Deficiency Affects Lipopolysaccharide-Induced Macrophage-Related Oxidative Stress And Myocardial Cell Apoptosis Via The Nrf2 Pathway Both In Vivo And In Vitro

Previous studies showed that interleukin-9 (IL-9) is involved in cardiovascular diseases, including hypertension and cardiac fibrosis. This study aimed to investigate the role of IL-9 in lipopolysaccharide (LPS)-induced myocardial cell (MC) apoptosis. Mice were treated with LPS, and IL-9 expression was measured and the results showed that compared with WT mice, LPS-treated mice exhibited increased cardiac Mo-derived IL-9. Additionally, the effects of IL-9 deficiency (IL-9-/-) on macrophage (Mo)-related oxidative stress and MC apoptosis were evaluated, the results showed that IL-9 knockout significantly exacerbated cardiac dysfunction, inhibited Nrf2 nuclear transfer, promoted an imbalance in M1 and M2 Mos, and exacerbated oxidative stress and MC apoptosis in LPS-treated mice. Treatment with ML385, a specific nuclear factor erythroid-2 related factor 2 (Nrf2) pathway inhibitor significantly alleviated the above effects in LPS-treated IL-9-/- mice. Bone marrow-derived Mos from wild-type (WT) mice and IL-9-/- mice were treated with LPS, and the differentiation and oxidative stress levels of Mos were measured. The effect of Mo differentiation on mouse MC apoptosis was also analyzed in vitro. The results showed that LPS-induced M1 Mo/M2 Mo imbalance and Mo-related oxidative stress were alleviated by IL-9 knockout but were exacerbated by ML385 treatment. The protective effects of IL-9 deficiency on the MC apoptosis mediated by LPS-treated Mos were reversed by ML-385. Our results suggest that deletion of IL-9 decreased the nuclear translocation of Nrf2 in Mos, which further aggravated Mo-related oxidative stress and MC apoptosis. IL-9 may be a target for the prevention of LPS-induced cardiac injury.