| Porcine circovirus disease is a immunosuppressive disease caused by porcine circovirus type2(PCV2). Since the outbreak of1990s, it has caused huge economic losses to pig industry throughout the world. PCV2can regulate a variety of signaling pathways, thus participates in cellullar immune response, inflammation and apoptosis. According to the literature, PCV2could activate p38MAPK and the nuclear factor-kappa B pathway, as well as change numerous cytokines expression in the cells.CD74is an integral membrane glycoprotein expressed on the surface of antigen presenting cells (APCs), which mainly involved in antigen presented and immune response. Recent studies suggest that CD74molecules can also play a role as an auxiliary signal molecule, for instance, as the specific receptors of the macrophage migration inhibitory factor (MIF) to involve in signal transduction of MIF, or directly involved in the follicular B cells mature and gathered at marginal zone of the B cells, and be as a gastric epithelial cell surface receptor in the process of helicobacter pylori infection to promote IL-8expression. In the complicated immune system, CD74molecules involved in all kinds of disease by regulating a variety of signaling pathways.Human CD74induces a signalling cascade that results in the activation of nuclear factor-kappa B (NF-κB); however, the functions of porcine CD74in PCV2pathogenic has not been widely studied. This study showed that porcine CD74is mainly expressed in cells of the macrophage lineage and can be induced by LPS, Poly (I:C) and infection with PCV2. In addition, it was confirmed that porcine CD74can activate NF-κB by promoting IκBα degradation and p65nuclear translocation. Furthermore, the transcription of NF-KB-regulated genes (IL-6, IL-8and COX-2) was upregulated in the response to the overexpression of porcine CD74. In general, porcine CD74significantly enhanced the inflammatory response by regulating the NF-κB signalling pathway during PCV2infection, which suggests that porcine CD74may be implicated in the pathogenesis of PCV2infection.1. The molecular characteristics of porcine CD74geneIt has been described the nucleic acid sequence and the amino acid sequence of porcine CD74through bioinformatics analysis, and phylogenetic tree was constructed after the amino acid sequence alignment of8species selected by the experiment. In addition, by using quantitative PCR, we showed that porcine CD74widely expressed in all the tested tissues and cells, but mainly in macrophage lineage, moderately in the immune system, while expressing quantity is the lowest in the pig kidney cells. Furthermore, the research of the subcellular localization of porcine CD74found that CD74located in the cytoplasm and mainly distributed in one place of the cytoplasm.2. The effect on CD74expression in PK15cells by LPS, Poly(I:C) and PCV2stimulationLPS, Poly (I:C) and PCV2stimulus was used to observe their effects on the expression of porcine CD74gene in PK15cells. The results confirmed that porcine CD74can be highly induced by LPS and Poly (I:C), and it was also significantly increases when PCV2infection.3. The regulation of porcine CD74to the NF-κB pathway in PCV2infectionIn the process of PCV2infection, overexpression of porcine CD74can promote the degradation of IκBα and p65nuclear translocation, so as to activate the NF-κB. CD74molecules and PCV2can alonely activate the NF-κB in PK-15cells, but the synergy of the two is likely to cause the NF-κB overactivation.4. The affects of porcine CD74to the IL-6, IL-8and COX-2expression in PCV2infectionIn this study, it was proved that the overexpression of porcine CD74can increase the expression of NF-KB-mediated downstream genes (IL-6, IL-8and of COX-2). Moreover, porcine CD74also can promote the proinflammatory cytokines production during the process of PCV2infection, strengthening the inflammatory response. |
PDF Full Text Request