Induction of colitis causes inflammatory responses in fat depots: Evidence for substance P pathways in human mesenteric preadipocytes

Iordanes Karagiannides, Efi Kokkotou, Morris Tansky, Tamara Tchkonia, Nino Giorgadza, Michael O'Brien, Susan E. Leeman, James L. Kirkland, Charalabos Pothoulakis

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

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-κB site lost their ability to respond to SP, indicating that SP-induced IL-8 expression is NF-κB-dependent. This report indicates that human mesenteric preadipocytes contain functional SP 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.

Original languageEnglish (US)
Pages (from-to)5207-5212
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number13
DOIs
StatePublished - Mar 28 2006

Keywords

  • Inflammatory bowel disease

ASJC Scopus subject areas

  • General

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