Tissue-specific regulation of glutamine synthetase gene expression in acute pancreatitis is confirmed by using interleukin-1 receptor knockout mice.
BACKGROUND
Acute pancreatitis causes a pronounced depletion of plasma and muscle glutamine pools. In several other catabolic disease states expression of the enzyme glutamine synthetase (GS) is induced in lung and muscle to support glutamine secretion by these organs. The hormonal mediators of GS induction have not been conclusively identified. We used mice deficient for the expression of the type 1 interleukin-1 receptor (IL-1R1 knockout mice) to investigate the expression of GS during acute edematous pancreatitis.


METHODS
Acute edematous pancreatitis was induced in adult male wild-type and IL-1R1 knockout mice by means of the intraperitoneal administration of cerulein, and their conditions were monitored. Five organs, including lung, liver, gastrocnemius muscle, spleen, and pancreas, were assayed for relative GS messenger RNA (mRNA) content by Northern blotting.


RESULTS
The ultimate severity of pancreatitis was reduced by IL-1R1 deficiency. GS mRNA levels increased during progression of pancreatitis in lung, spleen, and muscle tissue from each group. No consistent increase in GS mRNA level was observed in liver. IL-1R1 deficiency did not affect GS mRNA expression in lung tissue but consistently retarded GS induction in the spleens of knockout animals. IL-1R deficiency altered the kinetics of GS induction in muscle.


CONCLUSIONS
Cerulein-induced experimental pancreatitis causes an induction in GS mRNA levels in a tissue-specific fashion. IL-1R1 deficiency reduced the ultimate severity of the condition and altered the induction of GS mRNA in the spleen and muscle.
Abcouwer
S F
SF
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Norman
J
J
Fink
G
G
Carter
G
G
Lustig
R J
RJ
Souba
W W
WW
D000818:Animals; D015152:Blotting, Northern; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000201:enzymology; D010195:Pancreatitis / Q000201:enzymology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D013154:Spleen / Q000201:enzymology
D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D005974:Glutamate-Ammonia Ligase