ABSTRACT: The vitamin D receptor and inducible nitric oxide synthase associated pathways in the development of acquired resistance to Cooperia oncophora infection in cattle
Project description:Cooperia oncophora is an economically important gastrointestinal nematode in ruminants. Acquired resistance to Cooperia oncophora infection in cattle develops rapidly as a result of prior infections. Naïve cattle, when given a primary infection of high-dose infective L3 larvae, develop a strong immunity to subsequent reinfection. Compared to primary infection, reinfection resulted in a marked reduction in worm establishment. In order to understand molecular mechanisms underlying the development of acquired resistance, we characterized the transcriptomic responses of the bovine small intestine to a primary infection and reinfection. A total of 23 pathways were significantly impacted during infection. The vitamin D receptor activation was strongly induced only during reinfection, suggesting that this pathway may play an important role in the development of acquired resistance via its potential roles in immune regulation and intestinal mucosal integrity maintenance. The expression of inducible nitric oxide synthase (NOS2) was strongly induced during reinfection but now during primary infection. As a result, several canonical pathways associated with NOS2 were impacted. The genes involved in eicosanoid synthesis, including prostaglandin synthase 2 (PTGS2 or COX2), remained largely unchanged during infection. The rapid development of acquired resistance may help explain the lack of relative pathogenicity by Cooperia oncophora infection in cattle. Our findings will undoubtedly facilitate understanding of molecular mechanisms underlying the development of acquired resistance, which could have an important implication in vaccine design. The transcriptomic profiles of the bovine small intestine in response to both a primary infection and a drug-attenuated reinfection were compared. The data were analyzed using the same condition and procedure. The gene expression profiles of calves 14 days after a primary Cooperia oncophora infection and a drug-attenuated reinfection were compared to their respective age-matched controls (naive controls and drug-drenched worm-free controls)
Project description:Cooperia oncophora is an economically important gastrointestinal nematode in ruminants. Acquired resistance to Cooperia oncophora infection in cattle develops rapidly as a result of prior infections. Naïve cattle, when given a primary infection of high-dose infective L3 larvae, develop a strong immunity to subsequent reinfection. Compared to primary infection, reinfection resulted in a marked reduction in worm establishment. In order to understand molecular mechanisms underlying the development of acquired resistance, we characterized the transcriptomic responses of the bovine small intestine to a primary infection and reinfection. A total of 23 pathways were significantly impacted during infection. The vitamin D receptor activation was strongly induced only during reinfection, suggesting that this pathway may play an important role in the development of acquired resistance via its potential roles in immune regulation and intestinal mucosal integrity maintenance. The expression of inducible nitric oxide synthase (NOS2) was strongly induced during reinfection but now during primary infection. As a result, several canonical pathways associated with NOS2 were impacted. The genes involved in eicosanoid synthesis, including prostaglandin synthase 2 (PTGS2 or COX2), remained largely unchanged during infection. The rapid development of acquired resistance may help explain the lack of relative pathogenicity by Cooperia oncophora infection in cattle. Our findings will undoubtedly facilitate understanding of molecular mechanisms underlying the development of acquired resistance, which could have an important implication in vaccine design.
Project description:Identification of targets of SNO-CoA- and SCoR-mediated denitrosylation in HEK293 cells expressing inducible nitric oxide synthase.
Project description:The dysfunction of endothelial nitric oxide synthase may be involved in development of atherosclerosis; however, the underlying molecular and cellular mechanisms of atherosclerosis are poorly understood. Here, we investigated gene expressionsin relation to atherosclerosis using endothelial nitric oxide synthase (eNOS)-deficient mice.
Project description:The purpose of this study is to comprehensively elucidate the role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema using cap analysis of gene expression (CAGE) sequencing.
Project description:we found that inducible nitric oxide synthase (iNOS) is critical to this process by virtue of its ability to induce post-translational S-nitrosylation of epigenetic enzymes. The possible link between induction of PSC, S-nitrosylation and tissue regeneration remains largely unexplored. Here, we show that the inducible NO synthase (iNOS) translocates from the cytoplasm to the nucleus during regeneration of the zebrafish tailfin and that this is associated with alterations in the nuclear S-nitrosylome.
