title: Temporal response of liver signal transduction elements during in vivo endotoxin challenge in cattle: effects of growth hormone treatment.
abstract: We quantified the changes in abundance of inducible nitric oxide synthase (iNOS) and associated tissue signal transduction pathway elements (STPEs) in the bovine liver in response to lipopolysaccharide (LPS) challenge and further assessed the impact on the LPS-driven variable responses as affected by daily treatment with recombinant growth hormone (GH) prior to LPS challenge. Twenty-four cross-bred beef steers were divided into GH-treated (recombinant bovine GH, Monsanto Inc., St. Louis, MO; 0.1mg/kg BW, i.m., daily for 12 days) and non-GH-treatment (control) groups (n=12/group). Liver biopsy samples were obtained from all animals at 0, 3, 6, and 24h after LPS challenge (E. coli 055:B5, 2.5 microg/kg BW, i.v. bolus) for Western blot analyses of iNOS and STPEs. In response to LPS, tissue levels of iNOS increased significantly (P<0.001) in the first 3h and persisted at levels greater than those at time 0 until 24h. GH further augmented levels of iNOS at 0, 3, and 6h resulting in an overall significant increase in the iNOS protein level (P<0.01). AKT/protein kinase B (AKT/PKB) phosphorylation levels at time 0 were not different between GH-treated and control animals; LPS increased the phosphorylation of AKT/PKB with GH treatment stimulating a four-fold further increase of AKT/PKB phosphorylation. Effects similar to those on AKT/PKB were also observed on signal transducer and activator of transcription 5b (STAT5b). The family of mitogen-activated protein kinase (MAPK) showed different pattern of response. ERK1/2 phosphorylation increased 3h after LPS challenge but only in GH-treated group (P<0.01). Compared to 0 h, SAPK/JUN phosphorylation increased in both experimental groups 3, 6h (P<0.01), and 24h (P<0.05) after LPS. However, at 3h the increase was greater (P<0.01) in GH-treated than in control animals. No effect of LPS challenge or GH treatment on p38(MAPK) was observed. These results suggest that GH treatment has a significant impact on the differential activation of STPEs in the clinical response to LPS.
authors.affiliation: Growth Biology Laboratory, U.S. Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Building 200, Room 209, Beltsville, MD 20705, USA. cli@anri.barc.usda.gov
authors.forename: Cong-Jun
authors.initials: CJ
authors.lastname: Li
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Kahl
authors.forename: Donald
authors.initials: D
authors.lastname: Carbaugh
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Elsasser
mesh_terms: D000818:Animals; D002417:Cattle / Q000378:metabolism*; D004926:Escherichia coli; D013006:Growth Hormone / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D050799:STAT5 Transcription Factor; D013006:Growth Hormone; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3