Effects of protein malnutrition on IL-6-mediated signaling in the liver and the systemic acute-phase response in rats.
This study examines the effects of malnutrition on IL-6 signaling pathways of rats fed 2% vs. 20% casein diets for 14 days. Effects of malnutrition on the abundance and IL-6-stimulated phosphorylation of signaling proteins in the JAK-STAT and MAP kinase pathways were examined in the liver. Changes of the acute-phase response as reflected by serum alpha(1)-acid glycoprotein (AG), TNF-alpha (TNF), and IL-1beta (IL-1) were compared in the two dietary groups at 0, 4, 8, 16, and 24 h after IL-6 administration. Under basal conditions, the abundance of the IL-6 receptor, gp130, JAK1, STAT1, and STAT3 proteins and levels of phosphorylation of ERK1/2 and p38 were significantly increased in the liver in the 2% casein group compared with the 20% casein group. With IL-6 stimulation, the increased phosphorylation per unit of protein of these signaling proteins was not different in the liver between the two groups. Before IL-6 stimulation, serum levels of TNF, IL-1, IL-6, and AG were significantly higher in the 2% casein group than in the 20% casein group. After bolus injection of IL-6, changes in IL-1 and AG were similar in the two dietary groups, although a slight decline in AG level was noted after 8 h of IL-6 administration in the 2% protein group. These data demonstrate that protein malnutrition produces changes in inflammation-related proteins characteristic of a low-grade systemic inflammatory response and, thus, can serve as an inflammatory stimulus. The capacity for response to IL-6 is preserved, suggesting adaptive preservation of acute-phase responsiveness during malnutrition.
Ling
Pei-Ra
PR
Nutrition/Infection Laboratory, Rm. 569, 21-27 Burlington Bldg., Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA. pling@bidmc.harvard.edu
Smith
Robert J
RJ
Kie
Susanne
S
Boyce
Patricia
P
Bistrian
Bruce R
BR
D000210:Acute-Phase Reaction / Q000503:physiopathology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004032:Diet; D004435:Eating / Q000187:drug effects / Q000502:physiology; D015151:Immunoblotting; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D009961:Orosomucoid / Q000378:metabolism; D011233:Precipitin Tests; D011502:Protein-Energy Malnutrition / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D012709:Serum Albumin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D009961:Orosomucoid; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D012709:Serum Albumin; C494080:Stat1 protein, mouse; C494081:Stat1 protein, rat; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha