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

Aristea Sideri, Kyriaki Bakirtzi, David Q. Shih, Hon Wai Koon, Phillip Fleshner, Razvan Arsenescu, Violeta Arsenescu, Jerrold R. Turner, Iordanes Karagiannides, Charalabos Pothoulakis

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)420-432
Number of pages13
JournalCMGH
Volume1
Issue number4
DOIs
StatePublished - Jul 1 2015

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Substance P
Inflammatory Bowel Diseases
Adipocytes
Cytokines
Ulcerative Colitis
Interleukin-17
Messenger RNA
Crohn Disease
Colon
Fats
Interleukin Receptors
Biopsy
Neurokinin-1 Receptors
Neuropeptides
Mucous Membrane

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Sideri, Aristea ; Bakirtzi, Kyriaki ; Shih, David Q. ; Koon, Hon Wai ; Fleshner, Phillip ; Arsenescu, Razvan ; Arsenescu, Violeta ; Turner, Jerrold R. ; Karagiannides, Iordanes ; Pothoulakis, Charalabos. / Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients. In: CMGH. 2015 ; Vol. 1, No. 4. pp. 420-432.
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title = "Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients",
abstract = "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.",
author = "Aristea Sideri and Kyriaki Bakirtzi and Shih, {David Q.} and Koon, {Hon Wai} and Phillip Fleshner and Razvan Arsenescu and Violeta Arsenescu and Turner, {Jerrold R.} and Iordanes Karagiannides and Charalabos Pothoulakis",
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Sideri, A, Bakirtzi, K, Shih, DQ, Koon, HW, Fleshner, P, Arsenescu, R, Arsenescu, V, Turner, JR, Karagiannides, I & Pothoulakis, C 2015, 'Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients', CMGH, vol. 1, no. 4, pp. 420-432. https://doi.org/10.1016/j.jcmgh.2015.03.003

Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients. / Sideri, Aristea; Bakirtzi, Kyriaki; Shih, David Q.; Koon, Hon Wai; Fleshner, Phillip; Arsenescu, Razvan; Arsenescu, Violeta; Turner, Jerrold R.; Karagiannides, Iordanes; Pothoulakis, Charalabos.

In: CMGH, Vol. 1, No. 4, 01.07.2015, p. 420-432.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Substance P Mediates Proinflammatory Cytokine Release From Mesenteric Adipocytes in Inflammatory Bowel Disease Patients

AU - Sideri, Aristea

AU - Bakirtzi, Kyriaki

AU - Shih, David Q.

AU - Koon, Hon Wai

AU - Fleshner, Phillip

AU - Arsenescu, Razvan

AU - Arsenescu, Violeta

AU - Turner, Jerrold R.

AU - Karagiannides, Iordanes

AU - Pothoulakis, Charalabos

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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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U2 - 10.1016/j.jcmgh.2015.03.003

DO - 10.1016/j.jcmgh.2015.03.003

M3 - Article

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JO - Cellular and Molecular Gastroenterology and Hepatology

JF - Cellular and Molecular Gastroenterology and Hepatology

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