Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease.
Recent experimental data suggest that the idiosyncratic nature of drug-induced liver disease (DILD) may be due in part to a deficiency of one or more hepatoprotective factors. In this study we have investigated whether interleukin (IL)-6 may also be one of these factors. Following the induction of liver injury with acetaminophen (APAP), a time-dependent increase in liver mRNA expression of IL-6 and its family members IL-11, leukemia inhibitory factor, and oncostatin M was observed in wild type (WT) mice, suggesting a possible hepatoprotective role played by this cytokine family. Indeed, mice lacking IL-6 (IL-6-/-) were more susceptible than were WT mice to APAP-induced liver injury. The increased susceptibility of the IL-6-/- mice was associated with a deficiency in the expression of hepatic heat shock protein (HSP)25, 32, and 40 as well as inducible HSP70 following APAP treatment. These results suggest that IL-6 and possibly other family members may protect the liver from injury, at least in part, by up-regulating the hepatic expression of several cytoprotective HSPs.
Masubuchi
Yasuhiro
Y
Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, DHHS, Building 10, Room 8N110, Bethesda, MD 20892-1760, USA.
Bourdi
Mohammed
M
Reilly
Timothy P
TP
Graf
Mary Louise M
ML
George
John W
JW
Pohl
Lance R
LR
D000082:Acetaminophen; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D019610:Cytoprotection; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis
D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; D000082:Acetaminophen