An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD
An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD
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DOI：
10.1097/mib.0000000000000822
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发表时间：
2016-08-01
影响因子：
4.9
通讯作者：
Wick, Mary Jo
中科院分区：
文献类型：
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作者：
Brynjolfsson, Siggeir F.;Magnusson, Maria K.;Wick, Mary Jo
背景：骨髓细胞表达的触发受体 1 (TREM-1) 是炎症的有效放大器。最近，抗菌肽PGLYRP-1被证明是TREM-1的配体。在此，研究了抗 TREM-1 抗体抑制 IBD 患者结肠固有层细胞 (LPC) 释放促炎细胞因子的能力，并将其与 PGLYRP-1 水平相关。方法：将溃疡性结肠炎 (UC，n = 45) 或克罗恩病 (CD，n = 26) 患者的活检组织与因其他原因接受结肠镜检查的个体 (n = 17) 进行比较。通过流式细胞术分析骨髓细胞上的 TREM-1 表达。采用 LPC 进行细胞培养实验，分析 PGLYRP-1 和炎症细胞因子水平，并评估抗 TREM-1 对细胞因子分泌的影响。结果：炎症活检组织中表达 TREM-1 的中性粒细胞和募集的巨噬细胞的频率高于非炎症活检组织。炎症组织中的PGLYRP-1水平高于非炎症组织；它主要由中性粒细胞产生，其水平与促炎细胞因子的分泌相关。在抗 TREM-1 存在的情况下，用由 PGLYRP-1 与肽聚糖复合物组成的强效 TREM-1 激动剂刺激的 LPC 分泌的髓过氧化物酶、肿瘤坏死因子、白细胞介素 1 和白细胞介素 8 的分泌减少。此外，当用杀死的细菌刺激来自PGLYRP-1升高的炎症个体亚群的LPC时，抗TREM-1的阻断作用是明显的。结论：抗TREM-1抗体可以抑制PGLYRP-1升高的炎症患者促炎细胞因子的分泌。此外，PGLYRP-1 + 髓过氧化物酶是预测抗 TREM-1 治疗效果的潜在生物标志物。
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-, interleukin-1, 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.