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Title: TEMPORAL RESPONSE OF SIGNAL TRANSDUCTION ELEMENTS DURING ENDOTOXIN CHALLENGE IN CATTLE LIVER: EFFECTS OF GROWTH HORMONE TREATMENT

Author
item Li, Congjun - Cj
item KAHL, STANISLAW
item Carbaugh, Donald - Don
item ELSASSER, THEODORE

Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/15/2005
Publication Date: 2/8/2006
Citation: Li, C.J., Kahl, S., Carbaugh, D., Elsasser, T.H. 2006. Temporal response of signal transduction elements during endotoxin challenge in cattle liver cells: Effects of growth hormone treatment. Domestic Animal Endocrinology 32(2):79-92.

Interpretive Summary: To look into the effects of growth hormone on animal immune response to infection, we examined the expression of inducible nitric oxide synthase (iNOS) and the activities of potential signal transduction pathway elements in cattle liver cells in response to LPS challenge and the modification of these responses by daily treatment with recombinant GH daily treatment with recombinant growth hormone (GH) prior to Lipopolysaccharide (LPS) challenge. Animals (n=24) were divided into GH- and non GH-treatment groups (n=12/group) in a factorial arrangement of GH treatment (+/-) and biopsy sampling time. In responses to LPS challenge, the level of iNOS increased significantly in first three hrs and maintained at higher level thereafter to 24 hrs. In GH treated animals, the level of iNOS protein were increased at 0, 3, and 6 hr and significantly higher than that in non-GH treated animals. GH treatment stimulates the phosphorylation of Akt/Protein kinase B (PKB). Family of mitogen-activated protein kinases (MAPK), Erk, SAPK/JUK and p38 showed very different patterns of response. When the temporal profile of phospho-Erk only response to LPS in GH treated animals SAPK/JUN response to LPS in GH treated animals with significant higher level of phosphorylation than that in non-GH treated group. P38MAPK showed no temporal response to LPS in both groups. The possible mechanism of the augmentation of LPS-induced NO production by GH is discussed.

Technical Abstract: We examined the expression of inducible nitric oxide synthase (iNOS) and the activities of potential signal transduction pathway elements in cattle liver cells in response to LPS challenge and the modification of these responses by daily treatment with recombinant GH daily treatment with recombinant growth hormone (GH) prior to Lipopolysaccharide (LPS) challenge (LPS; 3.0 µg/kg BW, i.v. bolus, E. coli 055:B5). Animals (n=24) were divided into GH- and non GH-treatment groups (n=12/group, GH-treated (recombinant bovine GH, Monsanto Inc., 4 St. Louis, MO; 0.1 mg/kg BW, im, daily for 12 days, no LPS) in a factorial arrangement of GH treatment (+/-) and biopsy sampling time. In responses to LPS challenge, the level of iNOS increased significantly (P < 0.001) in first three hrs and maintained at higher level thereafter to 24 hrs. In GH treated animals, the level of iNOS protein were increased at 0, 3, and 6 hr and significantly higher than that in non-GH treated animals (P < 0.001). GH treatment stimulates the phosphorylation of Akt/Protein kinase B (PKB). Family of mitogen-activated protein kinases (MAPK), Erk, SAPK/JUK and p38 showed very different patterns of response. When the temporal profile of phospho-Erk only response to LPS in GH treated animals (P < 0.001), SAPK/JUN response to LPS in GH treated animals with significant higher level of phosphorylation (P < 0.001) than that in non-GH treated group. P38MAPK showed no temporal response to LPS in both groups. The possible mechanism of the augmentation of LPS-induced NO production by GH is discussed.