An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD.
Inflamm Bowel Dis
; 22(8): 1803-11, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-27243593
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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-1ß, 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.CONCLUSIONS:
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Colitis Ulcerosa
/
Enfermedad de Crohn
/
Citocinas
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Receptor Activador Expresado en Células Mieloides 1
/
Mucosa Intestinal
/
Anticuerpos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Inflamm Bowel Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Dinamarca