Thyroxine Affects Lipopolysaccharide-Induced Macrophage Differentiation and Myocardial Cell Apoptosis via the NF-B p65 Pathway Both In Vitro and In Vivo

Background. Numerous studies have demonstrated that the inflammatory response is involved in the progression of lipopolysaccharide- (LPS-) induced myocardial cell apoptosis. Accumulating evidence has shown that thyroxine participates in diseases by downregulating the inflammatory response. This study aimed at investigating whether thyroxine alleviates LPS-induced myocardial cell apoptosis. Methods. Bone marrow-derived macrophages (MO) were treated with LPS and thyroxine, and MO differentiation and MO-related cytokine expression were measured. The effect of MO differentiation on mouse cardiomyocyte (MCM) apoptosis was also detected in vitro. In addition, C57BL/6 mice underwent thyroidectomy and were treated with LPS 35 days later; subsequently, MO differentiation and myocardial cell apoptosis in hearts were analyzed. To determine whether the nuclear factor-kappa B (NF-B) p65 pathway mediates the effect of thyroxine on MO differentiation and myocardial cell apoptosis, the specific NF-B p65 pathway inhibitor JSH-23 was administered to mice that underwent a thyroidectomy. Results. Levothyroxine treatment significantly reduced the activation of the NF-B p65 pathway, decreased M1 macrophage (MO1) differentiation and MO1-related cytokine mRNA levels in LPS-treated MO, and increased M2 macrophage (MO2) differentiation and MO2-related cytokine mRNA expression. The protective effects of levothyroxine on MCM apoptosis mediated by LPS-treated MO were alleviated by JSH-23. In mice, thyroidectomy aggravated LPS-induced cardiac injury and cardiac dysfunction, further promoted NF-B p65 activation, and increased cardiac MO1 expression and myocardial cell apoptosis but decreased cardiac MO2 expression. JSH-23 treatment significantly ameliorated the thyroidectomy-induced increases in myocardial cell apoptosis and MO differentiation. Conclusions. Thyroxine alleviated the MO1/MO2 imbalance, reduced the inflammatory response, decreased myocardial cell apoptosis, and protected against cardiac injury and cardiac dysfunction in LPS-treated mice. Thyroxine may be a novel therapeutic strategy to prevent and treat LPS-induced cardiac injury.