title: An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD.
abstract: Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potent amplifier of inflammation. Recently, the antimicrobial peptide PGLYRP-1 was shown to be the ligand of TREM-1. Here, the ability of an anti-TREM-1 antibody to dampen the release of proinflammatory cytokines by colon lamina propria cells (LPCs) from patients with IBD was investigated and correlated with PGLYRP-1 levels.
  
  
  
  Biopsies from patients with ulcerative colitis (UC, n = 45) or Crohn's disease (CD, n = 26) were compared with those from individuals undergoing colonoscopy for other reasons (n = 17). TREM-1 expression was analyzed on myeloid cells by flow cytometry. Cell culture experiments with LPCs were used to analyze PGLYRP-1 and inflammatory cytokine levels and assess the effect of anti-TREM-1 on cytokine secretion.
  
  
  
  The frequency of TREM-1-expressing neutrophils and recruited macrophages was higher in inflamed than in noninflamed biopsies. The PGLYRP-1 level in inflamed tissue was higher than in noninflamed tissue; it was produced primarily by neutrophils, and its level correlated with the secretion of proinflammatory cytokines. Secretion of myeloperoxidase, tumor necrosis factor-α, interleukin-1β, and interleukin-8 by LPCs stimulated with the potent TREM-1 agonist consisting of PGLYRP-1 complexed with peptidoglycan was reduced in the presence of anti-TREM-1. Moreover, a blocking effect of anti-TREM-1 was apparent when LPCs from a subset of inflamed individuals with elevated PGLYRP-1 were stimulated with killed bacteria.
  
  
  
  An anti-TREM-1 antibody can dampen secretion of proinflammatory cytokines in inflamed patients with elevated PGLYRP-1. Moreover, PGLYRP-1 + myeloperoxidase is a potential biomarker for predicting the effect of anti-TREM-1 therapy.
authors.affiliation: *Department of Microbiology and Immunology, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;†Department of Internal Medicine and Clinical Nutrition, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;‡Novo Nordisk Research Center, Seattle, USA; and§Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Siggeir F
authors.initials: SF
authors.lastname: Brynjolfsson
authors.forename: Maria K
authors.initials: MK
authors.lastname: Magnusson
authors.forename: Philip L
authors.initials: PL
authors.lastname: Kong
authors.forename: Teis
authors.initials: T
authors.lastname: Jensen
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuijper
authors.forename: Katarina
authors.initials: K
authors.lastname: Håkansson
authors.forename: Christine B
authors.initials: CB
authors.lastname: Read
authors.forename: Vibeke W
authors.initials: VW
authors.lastname: Stennicke
authors.forename: Henrik
authors.initials: H
authors.lastname: Sjövall
authors.forename: Mary
authors.initials: M
authors.lastname: Jo Wick
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000906:Antibodies; D015415:Biomarkers; D016207:Cytokines; D053583:Interleukin-1beta; D016209:Interleukin-8; C491878:PGLYRP1 protein, human; D010457:Peptidoglycan; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase