title: Substance P mediates pro-inflammatory cytokine release form mesenteric adipocytes in Inflammatory Bowel Disease patients.
abstract: OBJECTIVE
  Substance P (SP), neurokinin-1 receptors (NK-1Rs) are expressed in mesenteric preadipocytes and SP binding activates proinflammatory signalling 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 to control human mesenteric preadipocytes. The Aim of our study is to investigate the effects of the neuropeptide SP on cytokine expression in preadipocytes of IBD vs control patients and evaluate 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 (CD) patients (n=10-11 per group). Preadipocytes were isolated, expanded in culture and exposed to substance P. Colon biopsies were obtained from control and IBD patients.
  
  
  RESULTS
  Tacr-1 and -2 mRNA were increased in IBD preadipocytes compared to controls, while Tac-1 mRNA was increased only in UC preadipocytes. SP differentially regulated the expression of inflammatory mediators in IBD preadipocytes compared to controls. Disease-dependent responses to SP were also observed between UC and CD preadipocytes. IL-17A mRNA expression and release increased after SP treatment in both CD and UC preadipocytes, while IL-17RA mRNA increased in colon biopsies 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 receptor in IBD colon opens the possibility of a fat-colonic mucosa inflammatory loop that may be active during IBD.
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA ; Postgraduate Program: "Molecular Medicine", University of Crete, Medical School, Greece.
authors.forename: Aristea
authors.initials: A
authors.lastname: Sideri
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Bakirtzi
authors.affiliation: F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: David Q
authors.initials: DQ
authors.lastname: Shih
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Hon Wai
authors.initials: HW
authors.lastname: Koon
authors.affiliation: F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Fleshner
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Hepatology & Nutrition, Wexner Medical Center, OSU, Columbus, OH 43210, USA.
authors.forename: Razvan
authors.initials: R
authors.lastname: Arsenescu
authors.affiliation: Inflammatory Bowel Diseases Center, Mucosal Immunology Lab, Division of Gastroenterology, Wexner Medical Center, OSU, Columbus , OH 43210, USA.
authors.forename: Violeta
authors.initials: V
authors.lastname: Arsenescu
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL 60637, USA ; Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Iordanes
authors.initials: I
authors.lastname: Karagiannides
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Charalabos
authors.initials: C
authors.lastname: Pothoulakis
keywords: Cytokines; Interleukin-17; Substance P; preadipocytes