期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 13, 页码 5207-5212出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0600821103
关键词
inflammatory bowel disease
资金
- NIDDK NIH HHS [R01 DK056891, DK 56891, DK 47343, R01 DK047343] Funding Source: Medline
Intracolonic administration of trinitrobenzene sulfonic acid in mice causes inflammation in the colon that is accompanied by increased expression of proinflammatory cytokines and of the substance P (SP), neurokinin 1 receptor (NK-1R) in the proximal mesenteric fat depot. We also investigated whether human mesenteric preadipocytes contain NK-1R and examined the functional consequences of exposure of these cells to SP as it relates to proinflammatory signaling. We found that human mesenteric preadipocytes express NK-1R both at the mRNA and protein levels. Exposure of human mesenteric preadipocytes to SP increased NK-1R mRNA and protein expression by 3-fold, and stimulated IL-8 mRNA expression and protein secretion. This effect was abolished when these cells were pretreated with the specific NK-1R antagonist CJ 012,255. Moreover, human mesenteric preadipocytes transfected with a luciferase promoter/reporter system containing the IL-8 promoter with a mutated NF-kappa B site lost their ability to respond to SP, indicating that SP-induced IL-8 expression is NF-kappa B-dependent. This report indicates that human mesenteric preadipocytes contain functional SIP receptors that are linked to proinflammatory pathways, and that SP can directly increase NK-1R expression. We speculate that mesenteric fat depots may participate in intestinal inflammatory responses via SP-NK-1R-related pathways, as well as other systemic responses to the presence of an ongoing inflammation of the colon.
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