Acute stress response in calorie-restricted rats to lipopolysaccharide-induced inflammation.
Calorie restriction (CR) reduces morbidity and mortality in a wide range of organisms, possibly through the stress response machinery. We analyzed the acute phase response of CR rats to lipopolysaccharide (LPS)-induced inflammatory challenge. Six-month-old male F344 rats, fed ad libitum (AL) or a 30% calorie-restricted diet from 6 weeks of age, received an intravenous LPS injection and were then sacrificed between 0 and 8 h. CR attenuated liver injury without reduction in the plasma concentrations of proinflammatory cytokines or nitric oxide (NO). Western blotting analysis of liver tissue demonstrated that CR did not affect the degradation of cytoplasmic I-kappaB and subsequent nuclear translocation of NF-kappaB, a key transcription factor after inflammatory challenge. We also analyzed the liver gene expression profiles at 0, 1 and 4 h with DNA arrays and cluster analysis. Compared with the AL group, CR upregulated the expression of several genes for inflammatory mediators or their related molecules at 0 h, but not at 1 or 4 h. CR downregulated genes for energy or xenobiotic metabolism and stress response proteins at 0 h. At 1 h, the relatively downregulated genes by CR were those for proteases and the ubiquitin-proteasome pathway. The present results suggest that CR attenuates liver injury without suppression of the proinflammatory response, and that the protective effect emerges from constitutively, rather than inductively, expressed gene products.
Tsuchiya
Tomoshi
T
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan.
Higami
Yoshikazu
Y
Komatsu
Toshimitsu
T
Tanaka
Kenji
K
Honda
Sumihisa
S
Yamaza
Haruyoshi
H
Chiba
Takuya
T
Ayabe
Hiroyoshi
H
Shimokawa
Isao
I
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D031204:Caloric Restriction; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000150:complications*; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism; D008297:Male; D005810:Multigene Family; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D013312:Stress, Physiological / Q000209:etiology*
D016207:Cytokines; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D000410:Alanine Transaminase