Infectious bacterial and viral diseases that cause hemolysis are considered life-threatening to grass carp (Ctenopharyngodon idellus), which is a species used in aquaculture worldwide. After heme and hemeproteins (Hb) are released as a result of hemolysis, the effect of excess Hb and heme on tissues remains to be characterized. To decipher the mechanisms, after incubation with Hb, we showed that lipopolysaccharide (LPS), Hb, and heme increased the cytotoxicity and secretion of inflammatory cytokines such as interleukin (IL)-6, chemokine (C-C motif) ligand 1 (CCL1), tumor necrosis factor (TNF)-α, IL-6, and IL-1β in vitro, which was due to stimulation of the expression of innate immune receptors, such as nucleotide-binding oligomerization domain (NOD2), toll-like receptor 2 (TLR2), TLR 4, and TLR3. The formation of reactive oxygen species (ROS) and the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB were important for increasing the cytokine production to induce heme, Hb, and LPS. Moreover, we confirmed that after LPS, Hb, and heme challenge, superoxide dismutase (SOD) and glutathione (GSH) synthetase (GSS) also caused remarkable destruction. However, catalase (CAT) and heme oxygenase-1 (HO-1) were strongly activated. In summary, our research findings present a framework through which heme and Hb concentrations amplify the secretions of inflammatory cytokines, which are induced by pattern recognition receptor (PRR) activation and present possible paths for immune intervention during infection with viral diseases and hemolytic bacterial.

导致溶血的传染性细菌和病毒性疾病被认为对草鱼（Ctenopharyngodon idellus)，这是一种在世界范围内用于水产养殖的物种。在由于溶血而释放血红素和血红素蛋白 (Hb) 后，过量 Hb 和血红素对组织的影响仍有待表征。为了破译这些机制，在与 Hb 孵育后，我们发现脂多糖 (LPS)、Hb 和血红素增加了细胞毒性和炎性细胞因子的分泌，例如白细胞介素 (IL)-6、趋化因子 (CC 基序) 配体 1 (CCL1)、体外肿瘤坏死因子 (TNF)-α、IL-6 和 IL-1β，这是由于刺激先天免疫受体的表达，如核苷酸结合寡聚结构域 (NOD2)、toll 样受体 2 ( TLR2)、TLR 4 和 TLR3。活性氧 (ROS) 的形成和丝裂原活化蛋白激酶 (MAPKs) 和核因子 (NF)-κB 的激活对于增加细胞因子的产生以诱导血红素、Hb 和 LPS 很重要。此外，我们证实在 LPS、Hb 和血红素攻击后，超氧化物歧化酶 (SOD) 和谷胱甘肽 (GSH) 合成酶 (GSS) 也造成了显着破坏。然而，过氧化氢酶 (CAT) 和血红素加氧酶-1 (HO-1) 被强烈激活。总之，我们的研究结果提出了一个框架，通过该框架，血红素和 Hb 浓度可放大由模式识别受体 (PRR) 激活诱导的炎性细胞因子的分泌，并为病毒性疾病和溶血性细菌感染期间的免疫干预提供了可能的途径。我们证实，在 LPS、Hb 和血红素攻击后，超氧化物歧化酶 (SOD) 和谷胱甘肽 (GSH) 合成酶 (GSS) 也造成了显着破坏。然而，过氧化氢酶 (CAT) 和血红素加氧酶-1 (HO-1) 被强烈激活。总之，我们的研究结果提出了一个框架，通过该框架，血红素和 Hb 浓度可放大由模式识别受体 (PRR) 激活诱导的炎性细胞因子的分泌，并为病毒性疾病和溶血性细菌感染期间的免疫干预提供了可能的途径。我们证实，在 LPS、Hb 和血红素攻击后，超氧化物歧化酶 (SOD) 和谷胱甘肽 (GSH) 合成酶 (GSS) 也造成了显着破坏。然而，过氧化氢酶 (CAT) 和血红素加氧酶-1 (HO-1) 被强烈激活。总之，我们的研究结果提出了一个框架，通过该框架，血红素和 Hb 浓度可放大由模式识别受体 (PRR) 激活诱导的炎性细胞因子的分泌，并为病毒性疾病和溶血性细菌感染期间的免疫干预提供了可能的途径。