4-苯基丁酸(4-PBA)抑制急性围产期炎症小鼠模型中性粒细胞募集

IF 3.6 3区 医学 Q2 IMMUNOLOGY
Journal of Immunology Research Pub Date : 2025-07-07 eCollection Date: 2025-01-01 DOI:10.1155/jimr/2438058
Christian Gille, Maylis Jungwirth, Silvia Pezer, Stefanie Dietz-Ziegler, Natascha Köstlin-Gille, Trim Lajqi
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引用次数: 0

摘要

中性粒细胞是第一个被招募到感染部位的免疫细胞,不受调节的激活与不良后果有关,特别是在早产儿中。因此,抑制中性粒细胞活性可能是预防急性和慢性炎症性疾病的一种手段;然而,对调节中性粒细胞活性的潜在药物知之甚少。4-苯基丁酸(4-PBA)是临床上常用的一种药物,作为化学伴侣抑制内质网应激,抑制免疫激活。在这里,我们研究了4-PBA调节中性粒细胞介导的炎症的潜力,特别是中性粒细胞的招募级联。我们发现,通过胎儿活体显微镜(IVM)评估,4-PBA抑制围产期中性粒细胞招募级联,以及中性粒细胞通过肌醇要求酶(IRE)-1α/细胞外信号调节激酶(ERK) 1/2信号通路通过内皮室的转运。同样,在体外实验中,4-PBA通过抑制骨髓中性粒细胞和内皮细胞中促炎介质的释放来促进抗炎表型。综上所述,我们的数据表明,4-PBA可以通过限制中性粒细胞过度浸润到炎症组织中来发挥抗炎作用,从而在治疗各种炎症性疾病方面具有重要的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

4-Phenyl Butyric Acid (4-PBA) Suppresses Neutrophil Recruitment in a Murine Model of Acute Perinatal Inflammation.

4-Phenyl Butyric Acid (4-PBA) Suppresses Neutrophil Recruitment in a Murine Model of Acute Perinatal Inflammation.

4-Phenyl Butyric Acid (4-PBA) Suppresses Neutrophil Recruitment in a Murine Model of Acute Perinatal Inflammation.

4-Phenyl Butyric Acid (4-PBA) Suppresses Neutrophil Recruitment in a Murine Model of Acute Perinatal Inflammation.

Neutrophils are the first immune cells to be recruited to the site of infection and deregulated activation is linked to adverse outcome, especially in premature neonates. Dampening neutrophil activity may therefore be a means of preventing acute and chronic inflammatory diseases; however, little is known about potential drugs to modulate neutrophil activity. 4-Phenyl butyric acid (4-PBA) is a clinically used drug, which acts as a chemical chaperone to inhibit endoplasmic reticulum (ER) stress and to suppress immune activation. Here, we investigated the potential of 4-PBA to regulate neutrophil-mediated inflammation and specifically the recruitment cascade of neutrophils. We found that 4-PBA suppressed perinatal neutrophil recruitment cascade as assessed by fetal intravital microscopy (IVM), as well as transmigration of neutrophils through the endothelial compartment via the inositol-requiring enzyme (IRE)-1α/extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. Likewise, 4-PBA promoted an anti-inflammatory phenotype by suppressing the release of pro-inflammatory mediators in bone marrow neutrophils and endothelial cells in vitro. Taken together, our data indicate that 4-PBA can exert anti-inflammatory effects by limiting excessive neutrophil infiltration into inflamed tissues, thereby holding significant therapeutic potential in managing various inflammatory diseases.

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来源期刊
CiteScore
6.90
自引率
2.40%
发文量
423
审稿时长
15 weeks
期刊介绍: Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology, molecular immunology, clinical immunology, cancer immunology, transplantation immunology, immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy.
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