Leptin: A pivotal mediator of intestinal inflammation in mice

被引:226
作者
Siegmund, B
Lehr, HA
Fantuzzi, G
机构
[1] Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Dept Med, Denver, CO 80262 USA
[2] Univ Mainz, Inst Pathol, D-6500 Mainz, Germany
关键词
D O I
10.1053/gast.2002.33631
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: In addition to acting as a regulator of food intake and energy expenditure, leptin can also modulate immune and inflammatory responses. The role of leptin in intestinal inflammation is the focus of the present study. Methods: Acute and chronic colitis were induced in leptin-deficient ob/ob or wild-type (WT) mice using dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS). The severity of colitis was evaluated, and possible mechanisms were studied. Results: Leptin directly stimulates intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs). In the DSS acute model, ob/ob mice exhibited a 72% reduction of colitis severity and spontaneous release of proinflammatory cytokines from the colon compared with WT mice. Replacement of leptin in ob/ob mice converted disease resistance to susceptibility, indicating that leptin deficiency, not obesity, accounts for the resistance to acute DSS-induced colitis. During chronic DSS-induced colitis and TNBS-induced colitis, in addition to reduced disease severity, ob/ob mice exhibited a significant attenuation in intestinal inflammation, accompanied by reduced production of cytokines and chemokines. When compared with WT mice, CD8(+) IELs of ob/ob mice were reduced in number as well as in their ability to synthesize interferon gamma. In addition, LPMCs of ob/ob mice showed increased apoptosis in untreated as well as DSS- or TNBS-treated mice. Phosphorylation of signal transducer and activator of transcription 3 and induction of cyclooxygenase 2 were absent in the colon of DSS-fed ob/ob mice. Conclusions: These results show that leptin represents a functional link between the endocrine and immune systems.
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页码:2011 / 2025
页数:15
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