Context: Tissue resident macrophages and peripherally infiltrating macrophages play a prominent role in maintaining homeostasis in the gastrointestinal tract (GIT), though aberrant activation is implicated in inflammatory conditions, including ulcerative colitis (UC). Recent metabolomic studies indicate that tyramine (TYR) is elevated in the stool of patients with UC. TYR activates the mammalian trace amine associated receptor 1 (TAAR1). Our previous work identified TAAR1 expression in mixed populations of immune cells, whereas a limited number of other studies have identified TAAR1-dependent effects in cytokine secretion and gene expression in T-cells and B-cells.Objective: To investigate whether TAAR1 may serve as a novel target for an anti-inflammatory therapeutic in UC, we explored TAAR1 expression in mouse bone marrow-derived macrophages (BMDMs), and its upregulation and activation in response to LPS and TYR.Results: Here, we demonstrate for the first time that TAAR1 is expressed in BMDM and undergoes agonist-induced upregulation. Additionally, TYR elicits significant increases in inflammatory cytokine gene expression in non-polarized and LPS-polarized BMDM, and the TAAR1 antagonist EPPTB inhibits the TYR-mediated upregulation of TAAR1 and inflammatory cytokine gene expression in BMDM. Conclusions: Our data suggest that TAAR1 is a mediator of macrophage inflammation and a potential therapeutic target to attenuate UC symptomology.

中文翻译：

---

痕量胺相关受体1（TAAR1）表达和小鼠骨髓源性巨噬细胞中炎性细胞因子产生的调节：溃疡性结肠炎炎症的一种新机制。

背景：尽管异常激活与包括溃疡性结肠炎（UC）在内的炎性疾病有关，但组织固有的巨噬细胞和周围浸润的巨噬细胞在维持胃肠道（GIT）的稳态中起着重要作用。最近的代谢组学研究表明，在UC患者的粪便中酪胺（TYR）升高。TYR激活哺乳动物微量胺相关受体1（TAAR1）。我们以前的工作确定了TAAR1在免疫细胞的混合群体中的表达，而有限的其他研究也已经发现TAAR1依赖性的影响T细胞和B细胞的细胞因子分泌和基因表达。 UC抗炎治疗的新靶标，我们研究了TAAR1在小鼠骨髓源巨噬细胞（BMDM）中的表达及其对LPS和TYR的响应的上调和激活。结果：在这里，我们首次证明TAAR1在BMDM中表达并经历激动剂诱导的上调。此外，TYR在非极化和LPS极化的BMDM中引起炎症细胞因子基因表达显着增加，而TAAR1拮抗剂EPPTB抑制TYR介导的TAAR1上调和BMDM中炎症细胞因子基因表达。结论：我们的数据表明TAAR1是巨噬细胞炎症的介质，并且是减轻UC症状的潜在治疗靶标。我们首次证明TAAR1在BMDM中表达并经历激动剂诱导的上调。此外，TYR在非极化和LPS极化的BMDM中引起炎症细胞因子基因表达显着增加，而TAAR1拮抗剂EPPTB抑制TYR介导的TAAR1上调和BMDM中炎症细胞因子基因表达。结论：我们的数据表明TAAR1是巨噬细胞炎症的介质，并且是减轻UC症状的潜在治疗靶标。我们首次证明TAAR1在BMDM中表达并经历激动剂诱导的上调。此外，TYR在非极化和LPS极化的BMDM中引起炎症细胞因子基因表达显着增加，而TAAR1拮抗剂EPPTB抑制TYR介导的TAAR1上调和BMDM中炎症细胞因子基因表达。结论：我们的数据表明TAAR1是巨噬细胞炎症的介质，并且是减轻UC症状的潜在治疗靶标。