Basic ResearchLeptin: A pivotal mediator of intestinal inflammation in mice☆,☆☆
Section snippets
Reagents
Recombinant murine leptin was purchased from R&D Systems, Inc. (Minneapolis, MN). RPMI and fetal calf serum were obtained from Life Technologies Inc. (Grand Island, NY). Concanavalin A (con A; type IV-S) was from Sigma Chemical Co. (St. Louis, MO).
Mice
Animal protocols were approved by the animal studies committee of the University of Colorado Health Sciences Center. Six- to 8-week-old female leptin-deficient (C57BL/6J ob/ob) mice and their wild-type (WT) lean littermates were obtained from Jackson
Leptin-stimulated LPMCs and IELs in vitro
To evaluate the direct stimulatory effect of leptin on the LPMC and IEL population, the following experiments were conducted. LPMCs were isolated from the colons of healthy C57BL/6 mice and cultured in the absence or presence of leptin (100 ng/mL) or con A (0.5 μg/mL; Figure 1A).
Discussion
In the present study, leptin was identified as a critical mediator of intestinal inflammation. Leptin-deficient ob/ob mice were found to be resistant to acute and chronic intestinal inflammation induced by DSS as well as to colitis induced by rectal administration of TNBS. In IELs and LPMCs, leptin stimulation resulted in STAT-3 activation. In addition, stimulation of LPMCs with leptin induced IL-18 production, indicating a direct effect of leptin on these cell populations. The resistance to
Acknowledgements
The authors thank Charles A. Dinarello for his support and critical review of the manuscript and Massimo Gadina for the detailed instructions for the immunoprecipitation.
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Address requests for reprints to: Giamila Fantuzzi, Ph.D., Division of Infectious Diseases, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, B168, Denver, Colorado 80262. e-mail: [email protected]; fax: (303) 315-8054.
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Supported by the Broad Medical Foundation and the Deutsche Forschungsgemeinschaft DFG SI 749/2-1 (to B.S.).