Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression.
Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P < 0.05), tumour necrosis factor-alpha (TNF-alpha) and nitrites (P < 0.01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-alpha. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.
Granado
M
M
Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain.
Martín
A I
AI
Priego
T
T
Villanúa
M A
MA
López-Calderón
A
A
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005682:Gadolinium / Q000494:pharmacology*; D006505:Hepatitis / Q000378:metabolism* / Q000473:pathology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018972:Insulin-Like Growth Factor Binding Protein 3; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D005682:Gadolinium; C038958:gadolinium chloride