Up-regulation of IL-18BP, but not IL-18 mRNA in rat liver by LPS.
Interleukin (IL)-18 is a pro-inflammatory cytokine that plays a critical role in inflammation leading to liver damage, through promotion of Fas-mediated apoptosis. Inhibition of IL-18 activity protects against LPS-induced lethality in mice and against liver damage induced by LPS after sensitisation of mice with Proprionibacterium acnes. A specific, potent, endogenous inhibitor of IL-18 (IL-18BP) has been identified in mice and humans, and IL-18BP mRNA is expressed constitutively in liver. The objectives of this study were to compare changes in IL-1beta and IL-18 mRNA expression in the liver of rats in response to peripheral injection of LPS, using real-time PCR, and also to investigate whether IL-18BP mRNA expression is affected by this treatment. LPS rapidly up-regulated IL-1beta mRNA expression, but IL-18 mRNA expression was unaffected by LPS treatment. Unlike IL-18, IL-18BP mRNA was up-regulated dramatically by approximately 12-fold above nai;ve levels, peaking 3 h after LPS injection. This ability of LPS to up-regulate expression of the endogenous IL-18 inhibitor may indicate a mechanism by which the inflammatory response to LPS is regulated.
Wheeler
Rachel D
RD
School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK. rachel.wheeler@mail.mcgill.ca
Young
Elizabeth A
EA
Rothwell
Nancy J
NJ
Hall
Matthew D
MD
Luheshi
Giamal N
GN
D000818:Animals; D006023:Glycoproteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D020382:Interleukin-18; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C118370:interleukin-18 binding protein