title: C1q/TNF-related protein-3 (CTRP-3) is secreted by visceral adipose tissue and exerts antiinflammatory and antifibrotic effects in primary human colonic fibroblasts.
abstract: BACKGROUND
  The adipokine CTRP-3 (C1q/TNF-related protein-3) belongs to the C1q/TNF-related protein family which antagonizes the effects of lipopolysaccharide (LPS). The aim was to investigate the antiinflammatory and antifibrotic role of CTRP-3 in Crohn's disease (CD).
  
  
  METHODS
  Mesenteric adipose tissue (MAT) of patients with CD or colonic cancer (CC) was resected. Human primary colonic lamina propria fibroblasts (CLPF) were isolated from controls and CD patients. Concentrations of chemokines and cytokines in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Expression of connective tissue growth factor (CTGF), collagen I, and collagen III was analyzed by real-time polymerase chain reaction (PCR). Recombinant CTRP-3 expressed in insect cells was used for stimulation experiments.
  
  
  RESULTS
  CTRP-3 is synthesized and secreted by MAT resected from patients with CD, ulcerative colitis (UC), CC, and sigma diverticulitis as well as by murine and human mature adipocytes. CTRP-3 had no effect on the basal secretion of MCSF, MIF, or RANTES in MAT of CD and control patients. LPS-stimulation (10 ng/mL) significantly increased IL-8 release in CLPF of CD patients and, to a lesser extent, in cells of controls and of fibrotic CD tissue. CTRP-3 significantly and dose-dependently reduced LPS-induced IL-8 secretion in CLPF within 8 hours after LPS exposure, whereas LPS-induced IL-6 and TNF release was not affected. CTRP-3 inhibited TGF-β production and the expression of CTGF and collagen I in CLPF, whereas collagen III expression remained unchanged.
  
  
  CONCLUSIONS
  CTRP-3 exerts potent antiinflammatory and antifibrotic effects in CLPF by antagonizing the LPS pathway and by targeting the TGF-β-CTGF-collagen I pathway.
authors.affiliation: Department of Internal Medicine I, University Medical Center Regensburg, Germany. claudia.hofmann@klinik.uni-regensburg.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Hofmann
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Florian
authors.initials: F
authors.lastname: Obermeier
authors.forename: Gisela
authors.initials: G
authors.lastname: Paul
authors.forename: Christa
authors.initials: C
authors.lastname: Büchler
authors.forename: Andrea
authors.initials: A
authors.lastname: Kopp
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäffler
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D048069:Tumor Necrosis Factors / Q000494:pharmacology*
chemical_list: D054392:Adipokines; D000893:Anti-Inflammatory Agents; C506069:C1QTNF3 protein, human; D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors