Basic–Alimentary TractLeptin mediates Clostridium difficile toxin A–induced enteritis in mice☆,☆☆
Section snippets
Materials and methods
Toxin A was purified from culture supernatants of C. difficile strain 10,463 as previously described.30 Protein concentrations were determined with the DC protein assay (Bio-Rad Laboratories, Hercules, CA).
Reduced toxin A–induced fluid secretion and intestinal inflammation in leptin-deficient and leptin-resistant mice
To assess directly the role of leptin in the toxin A model of intestinal inflammation, we injected ileal loops of anesthetized wild-type, leptin-deficient (ob/ob), and leptin-resistant (db/db) mice, with either buffer or purified toxin A and, after 4 hours, we measured toxin A–associated ileal responses. Basal fluid secretion in response to buffer injection was comparable between wild-type and ob/ob and db/db mice (Figure 1A).
Discussion
We have reported previously that C. difficile toxin A stimulates fluid secretion and elicits an acute inflammatory response in animal intestine characterized by neutrophil infiltration and epithelial cell destruction.5 The results presented here show that animals either genetically lacking leptin itself or resistant to leptin's effects have substantially reduced responses to toxin A, which is normalized in response to the administration of leptin in leptin-deficient ob/ob mice but not in
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Supported by research grants PO DK33506 (to C.P.), PO 1 DK 56116 (to C.M.), RO1 DK 58785 (to C.M.), MO RR 01032 (to C.M.), and a Pilot Feasibility Study from P30 DK 40561 from the National Institutes of Health. This study also was supported by a research grant from the Crohn's and Colitis Foundation.
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Address requests for reprints to: Charalabos Pothoulakis, M.D., Beth Israel Deaconess Medical Center, Division of Gastroenterology, Dana 501, 330 Brookline Avenue, Boston, Massachusetts 02215. e-mail: [email protected]; fax: (617) 667-2767.