Hemeprotein amplifies the innate immune receptors of Ctenopharyngodon idellus kidney cells through NF-κB- and MAPK-dependent reactive oxygen species generation

The Oxidative Injury of Extracellular Hemoglobin Is Associated With Reactive Oxygen Species Generation of Grass Carp (Ctenopharyngodon idella)

“…According to previous studies, Hb or heme could induce inflammatory reactions via a Toll-like receptor 4 (TLR4)-dependent mechanism in macrophages ( 46 ), NF-κB activation in endothelial cells ( 47 , 48 ), and leucine-rich repeat-containing protein 3 (NLRP3) in both macrophages and endothelial cells ( 48 , 49 ). In CIK cells, we also found that the incubation of heme protein increased the secretion of inflammatory cytokines such as IL-6 , CCL1 , TNF-α , and IL-1β ( 25 ). In this study, the PHZ-induced hemolysis significantly increased the expressions of the cytokine-related genes in the head kidney; however, the expression pattern of these cytokine-related genes showed some differences.…”

“…Previous studies revealed that the oxidized Hb releases heme, and the generation of free radicals by the Fenton reaction has been considered the major form of ROS generation by heme and an important mechanism of heme-induced cytotoxicity ( 40 , 44 ). Our previous studies also revealed that Hb activated the MAPK and NF-κB pathways to generate ROS, resulting in oxidative damage to CIK cells ( 25 ). The results from this study also revealed that the PHZ-induced hemolysis obviously increased the production of ROS in both head and middle kidney.…”

“…The generated reactive oxygen species (ROS) showed strong bactericidal activity (26). Our further studies also revealed that the grass carp Hb increased the cytotoxicity and secretion of inflammatory cytokines and activated mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kB) pathways to generate ROS, resulting in oxidative damage to C. idellus kidney (CIK) cells (25,27). However, the mechanism of hemolysis-induced tissue injury in teleost is still not clear.…”

“…The continuous expansion of the breeding scale and density of aquaculture, coupled with the deterioration of the breeding environment, all significantly increased the frequency of various bacterial or viral infections, leading to deaths and economic losses. The infection of hemorrhagic pathogens such as Aeromonas hydrophila or grass carp reovirus (GCRV) in grass carp causes hemolysis and releases excess Hb to plasma or tissues, which may pose a serious threat to fish health ( 25 ). In a previous study, we have demonstrated that the cell-free Hb released from grass carp RBCs could quickly be auto-oxidated to Hb-Fe 3+ in the presence of oxygen (O 2 ) and release superoxide radical (O 2−.…”

Structural characterization and immunomodulatory effects of extracellular polysaccharide from Lactobacillus paracasei VL8 obtained by gradient ethanol precipitation

“…Polysaccharides are macromolecular compounds that cannot be directly accessed by cells. Instead, they need to be recognized by pattern recognition receptors on the surface of macrophages, which in turn activate relevant signaling pathways, enhance the phagocytic activity of cells and promote the secretion of active substances such as NO to exert immunomodulatory functions (Lu et al., 2021). Our findings showed that within a certain concentration range, the activation of VL8‐EPS50 was significantly higher than the other two fractions.…”