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

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69 Scopus citations


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
Issue number13
StatePublished - Mar 28 2006


  • Inflammatory bowel disease

ASJC Scopus subject areas

  • General

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