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Open Access Publications from the University of California

Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients

  • Author(s): Sideri, A
  • Bakirtzi, K
  • Shih, DQ
  • Koon, HW
  • Fleshner, P
  • Arsenescu, R
  • Arsenescu, V
  • Turner, JR
  • Karagiannides, I
  • Pothoulakis, C
  • et al.

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© 2015 The Authors. Background & Aims: Substance P (SP) neurokinin-1 receptors (NK-1Rs) are expressed in mesenteric preadipocytes, and SP binding activates proinflammatory signaling in these cells. We evaluated the expression levels of SP (Tac-1), NK-1R (Tacr-1), and NK-2R (Tacr-2) mRNA in preadipocytes isolated from patients with inflammatory bowel disease (IBD) and examined their responsiveness to SP compared with control human mesenteric preadipocytes. We investigated the effect of the neuropeptide SP on cytokine expression in preadipocytes of IBD versus control patients and evaluated the potential effects of these cells on IBD pathophysiology via SP-NK-R interactions. Methods: Mesenteric fat was collected from control, ulcerative colitis (UC) and Crohn's disease patients (n = 10-11 per group). Preadipocytes were isolated, expanded in culture, and exposed to substance P. Colon biopsy samples were obtained from control and IBD patients. Results: Tacr-1 and -2 mRNA were increased in IBD preadipocytes compared with controls, but Tac-1 mRNA was increased only in UC preadipocytes. SP differentially regulated the expression of inflammatory mediators in IBD preadipocytes compared with controls. Disease-dependent responses to SP were also observed between Crohn's disease and UC preadipocytes. Interleukin 17A (IL-17A) mRNA expression and release increased after SP treatment in both Crohn's disease and UC preadipocytes; IL-17RA mRNA increased in colon biopsies samples from IBD patients. Conclusions: Preadipocyte SP-NK-1R interactions during IBD may participate in IBD pathophysiology. The ability of human preadipocytes to release IL-17A in response to SP together with increased IL-17A receptors in the IBD colon suggests that a fat-colonic mucosa inflammatory loop may be active during IBD.

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