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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/G76    most recent 00053.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Liu, S. X. L. Articles by De Plaen, I. G. PubMed PubMed Citation Articles by Liu, S. X. L. Articles by De Plaen, I. G.

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Platelet-activating factor induces the processing of nuclear factor-B p105 into p50, which mediates acute bowel injury in mice

Departments of ¹Pediatrics (Neonatology) and ²Pathology, Children's Memorial Research Center, Northwestern University Feinberg School of Medicine (Medical School), Chicago, Illinois

Submitted 10 February 2009 ; accepted in final form 14 May 2009

Platelet-activating factor (PAF), an endogenous proinflammatory phospholipid, when injected intravascularly to rats and mice, causes shock, acute bowel injury, and a rapid activation of NF-B p50-p50 with upregulation of the chemokine CXCL2 in the intestine. In this study, we investigate the mechanism of NF-B activation and the role of the NF-B p50 subunit in PAF-induced shock and acute bowel injury. NF-B p50-deficient mice and wild-type mice were anesthetized and tracheotomized, and their carotid artery was cannulated for blood pressure monitoring, blood sampling, and PAF administration. For determination of bowel injury, shock, and survival, PAF (2.2 µg/kg, intra-arterially, i.a.) was injected. Two hours later, animals were euthanized, and their small intestines were removed for histological examination. For biochemical studies, PAF (1.5 µg/kg i.a.) was administered and the small intestine removed after 15–60 min. We found that PAF induced an increase in p105 processing within 30 min, but there were no changes in the levels of the NF-B inhibitory proteins IB and β. NF-B p50-deficient mice were protected against PAF-induced mortality, shock, intestinal hypoperfusion, and injury compared with wild-type animals. We also found that p50-deficient mice had decreased gene expression of CXCL2 and TNF and a decrease in CXCL2 protein production compared with wild-type mice. Our study suggests that PAF increases the processing of NF-B p105 into p50, with upregulation of proinflammatory cytokines, which leads to PAF-induced systemic inflammatory response and acute bowel injury.

intestine; necrotizing enterocolitis