Immune-enhancing enteral nutrients differentially modulate the early proinflammatory transcription factors mediating gut ischemia/reperfusion.
BACKGROUND
Recent reports suggest that enteral diets enriched with arginine may be harmful by enhancing inflammation. This is consistent with our gut ischemia/reperfusion (I/R) model in which arginine induced the proinflammatory mediator inducible nitric oxide synthase and resulted in injury and inflammation whereas glutamine was protective. We now hypothesize that arginine and glutamine differentially modulate the early proinflammatory transcription factors activated by gut I/R.


METHODS
At laparotomy, jejunal sacs were filled with either 60 mmol/L glutamine, arginine, or an iso-osmotic control followed by 60 minutes of superior mesenteric artery occlusion and 6 hours of reperfusion and compared with shams. Jejunum was harvested for nuclear factor (NF)-kappaB and activator protein-1 (AP-1) measured by electrophoretic mobility shift assay and c-jun and c-fos (AP-1 family) by supershift.


RESULTS
Both NF-kappaB and AP-1 were activated by gut I/R. Arginine and glutamine had no differential effect on NF-kappaB, whereas AP-1 expression (c-jun but not c-fos) was markedly enhanced by arginine and significantly lessened by glutamine.


CONCLUSIONS
Arginine enhanced expression of the early proinflammatory transcription factor AP-1 but not NF-kappaB. This represents a novel mechanism by which arginine may be harmful when administered to critically ill patients.
Sato
Norio
N
Department of Surgery, University of Texas-Houston, Houston, Texas 77030, USA.
Moore
Frederick A
FA
Smith
Marshall A
MA
Zou
Lei
L
Moore-Olufemi
Stacey
S
Schultz
Stanley G
SG
Kozar
Rosemary A
RA
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000276:immunology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D024202:Electrophoretic Mobility Shift Assay; D004750:Enteral Nutrition / Q000009:adverse effects / Q000379:methods*; D005973:Glutamine / Q000276:immunology / Q000627:therapeutic use*; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D007249:Inflammation; D007583:Jejunum / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D008297:Male; D017538:Mesenteric Artery, Superior; D008641:Mesenteric Vascular Occlusion / Q000150:complications / Q000276:immunology / Q000628:therapy*; D016328:NF-kappa B / Q000032:analysis / Q000187:drug effects* / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D018579:Patient Selection; D047492:Peroxisome Proliferator-Activated Receptors / Q000032:analysis / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000276:immunology / Q000628:therapy*; D012307:Risk Factors; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000187:drug effects* / Q000276:immunology
D007155:Immunologic Factors; D016328:NF-kappa B; D047492:Peroxisome Proliferator-Activated Receptors; D018808:Transcription Factor AP-1; D005973:Glutamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat