Liu Lu, Chen Junsheng, Deng Yajie, Gao Fei, Lin Ting, Yang Zhijun, Chen Daijie, Yin Yu
School of Pharmaceutical Sciences, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, China.
National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry, No. 285 Gebaini Road, Pudong New Area, Shanghai, 200120, China.
J Antibiot (Tokyo). 2025 May 9. doi: 10.1038/s41429-025-00825-8.
Contezolid, a novel oxazolidinone antibiotic, has comparable or superior antibacterial efficacy and safety to linezolid, now widely used for treating multidrug-resistant Gram-positive bacterial infections. Although numerous studies have investigated the immunomodulatory effects of oxazolidinone antibiotics, the immunomodulatory properties of contezolid remain poorly understood. This study aimed to investigate the anti‑inflammatory effects of contezolid using LPS-stimulated RAW264.7 macrophages. Experimental assessments demonstrated that contezolid significantly suppressed key inflammatory mediators, including nitric oxide and reactive oxygen species, while reducing IL-6 and TNF-α cytokine levels and CD86 concurrently. Functional analysis revealed attenuated phagocytic activity through fluorescence-based bacterial internalization assays and viable bacterial colony counting. Mechanistic studies using qRT-PCR identified transcriptional downregulation of Toll-like receptors, with TLR2 showing particularly pronounced suppression compared to activated controls. These findings indicate that, in addition to its known antimicrobial activity, contezolid also exhibits anti-inflammatory properties.
康替唑胺是一种新型恶唑烷酮类抗生素,其抗菌疗效和安全性与目前广泛用于治疗耐多药革兰氏阳性菌感染的利奈唑胺相当或更优。尽管已有大量研究探讨了恶唑烷酮类抗生素的免疫调节作用,但康替唑胺的免疫调节特性仍知之甚少。本研究旨在利用脂多糖刺激的RAW264.7巨噬细胞研究康替唑胺的抗炎作用。实验评估表明,康替唑胺可显著抑制关键炎症介质,包括一氧化氮和活性氧,同时降低白细胞介素-6和肿瘤坏死因子-α细胞因子水平以及共刺激分子CD86的表达。功能分析通过基于荧光的细菌内化试验和活菌菌落计数揭示了吞噬活性减弱。使用qRT-PCR的机制研究确定了Toll样受体的转录下调,与激活的对照相比,Toll样受体2的抑制尤为明显。这些发现表明,除了已知的抗菌活性外,康替唑胺还具有抗炎特性。