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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Anti-Inflammatory benefits of antibiotic-induced neutrophil apoptosis: tulathromycin induces caspase-3-dependent neutrophil programmed cell death and inhibits NF-kappaB signaling and CXCL8 transcription.
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Anti-Inflammatory benefits of antibiotic-induced neutrophil apoptosis: tulathromycin induces caspase-3-dependent neutrophil programmed cell death and inhibits NF-kappaB signaling and CXCL8 transcription.

机译：抗生素诱导的中性粒细胞凋亡的抗炎作用：图拉霉素诱导caspase-3依赖性中性粒细胞程序性细胞死亡，并抑制NF-κB信号传导和CXCL8转录。

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Clearance of apoptotic neutrophils is a central feature of the resolution of inflammation. Findings indicate that immuno-modulation and induction of neutrophil apoptosis by macrolide antibiotics generate anti-inflammatory benefits via mechanisms that remain obscure. Tulathromycin (TUL), a new antimicrobial agent for bovine respiratory disease, offers superior clinical efficacy for reasons not fully understood. The aim of this study was to identify the immuno-modulating effects of tulathromycin and, in this process, to establish tulathromycin as a new model for characterizing the novel anti-inflammatory properties of antibiotics. Bronchoalveolar lavage specimens were collected from Holstein calves 3 and 24 h postinfection, challenged intratracheally with live Mannheimia haemolytica (2 x 10(7) CFU), and treated with vehicle or tulathromycin (2.5 mg/kg body weight). Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) revealed that tulathromycin treatment significantly increased leukocyte apoptosis and reduced levels of proinflammatory leukotriene B(4) in M. haemolytica-challenged calves. In vitro, tulathromycin concentration dependently induced apoptosis in freshly isolated bovine neutrophils from healthy steers in a capase-3-dependent manner but failed to induce apoptosis in bovine fibroblasts, epithelial cells, and endothelial cells, as well as freshly isolated bovine blood monocytes and monocyte-derived macrophages. The proapoptotic effects of TUL were also, in part, drug specific; equimolar concentrations of penicillin G, oxytetracycline, and ceftiofur failed to cause apoptosis in bovine neutrophils. In addition, tulathromycin significantly reduced levels of phosphorylated IkappaBalpha, nuclear translocation of NF-kappaB p65, and mRNA levels of proinflammatory interleukin-8 in lipopolysaccharide (LPS)-stimulated bovine neutrophils. The findings illustrate novel mechanisms through which tulathromycin confers anti-inflammatory benefits.
机译：凋亡中性粒细胞的清除是炎症消退的主要特征。研究结果表明，大环内酯类抗生素通过免疫调节和中性粒细胞凋亡诱导，通过仍不清楚的机制产生抗炎作用。 Tulathromycin（TUL）是一种用于牛呼吸道疾病的新型抗菌药物，由于尚未完全了解的原因，其可提供卓越的临床疗效。这项研究的目的是确定图拉霉素的免疫调节作用，并在此过程中建立图拉霉素作为表征新型抗生素抗炎特性的新模型。感染后3和24小时从荷斯坦牛犊收集支气管肺泡灌洗标本，气管内用活的溶血曼海姆菌（2 x 10（7）CFU）进行气管激发，并用媒介物或土拉霉素（2.5 mg / kg体重）处理。终端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）染色和酶联免疫吸附测定（ELISA）显示，图拉霉素治疗显着增加了溶血支原体攻击小牛的白细胞凋亡并降低了促炎性白三烯B（4）的水平。在体外，图拉霉素浓度以capase-3依赖性方式诱导健康ste牛新鲜分离的嗜中性白细胞中的细胞凋亡，但未能诱导牛成纤维细胞，上皮细胞和内皮细胞以及新鲜分离的牛血单核细胞和单核细胞凋亡衍生的巨噬细胞。 TUL的促凋亡作用也部分是药物特异性的。等摩尔浓度的青霉素G，土霉素和头孢噻呋不能引起牛中性粒细胞凋亡。此外，图拉霉素显着降低了脂多糖（LPS）刺激的牛中性粒细胞中磷酸化的IkappaBalpha的水平，NF-κBp65的核易位以及促炎性白介素8的mRNA水平。这些发现说明了图拉霉素可赋予抗炎作用的新机制。

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