Park Ga Young, Lee Hye Min, Yu Hyun Jin, Son Jee Soo, Park Sang Joon, Song Kyoung Seob
Department of Physiology, Kosin University College of Medicine, 34 Amnam-dong, Seo-gu, Busan, 49267, South Korea.
Institute of Life Technology, iNtRON Biotechnology, Seongnam, South Korea.
Genes Genomics. 2018 Dec;40(12):1383-1388. doi: 10.1007/s13258-018-0755-4. Epub 2018 Oct 23.
The development of therapeutic bacteriophages will provide several benefits based on an understanding the basic physiological dynamics of phage and bacteria interactions for therapeutic use in light of the results of antibiotic abuse. However, studies on bacteriophage therapeutics against microbes are very limited, because of lack of phage stability and an incomplete understanding of the physiological intracellular mechanisms of phage. The major objective of this investigation was to provide opportunity for development of a novel therapeutic treatment to control respiratory diseases in swine. The cytokine array system was used to identify the secreted cytokines/chemokines after Bordetella bronchiseptica infection into swine nasal turbinate cells (PT-K75). We also performed the real-time quantitative PCR method to investigate the gene expression regulated by B. bronchiseptica infection or bacteriophage treatment. We found that B. bronchiseptica infection of PT-K75 induces secretion of many cytokines/chemokines to regulate airway inflammation. Of them, secretion and expression of IL-1β and IL-6 are increased in a dose-dependent manner. Interestingly, membrane-bound mucin production via expression of the Muc1 gene is increased in B. bronchiseptica-infected PT-K75 cells. However, cytokine production and Muc1 gene expression are dramatically inhibited by treatment with a specific B. bronchiseptica bacteriophage (Bor-BRP-1). The regulation of cytokine profiles in B. bronchiseptica-induced inflammation by B. bronchiseptica bacteriophage is essential for avoiding inappropriate inflammatory responses. The ability of bacteriophages to downregulate the immune response by inhibiting bacterial infection emphasizes the possibility of bacteriophage-based therapies as a novel anti-inflammatory therapeutic strategy in swine respiratory tracts.
鉴于抗生素滥用的结果，基于对噬菌体与细菌相互作用基本生理动力学的理解，治疗性噬菌体的开发将带来诸多益处，可用于治疗用途。然而，由于噬菌体稳定性不足以及对其生理细胞内机制的理解不完整，针对微生物的噬菌体治疗研究非常有限。本研究的主要目的是为开发一种控制猪呼吸道疾病的新型治疗方法提供机会。使用细胞因子阵列系统来鉴定支气管败血波氏杆菌感染猪鼻甲骨细胞（PT-K75）后分泌的细胞因子/趋化因子。我们还采用实时定量PCR方法来研究支气管败血波氏杆菌感染或噬菌体处理所调节的基因表达。我们发现，PT-K75细胞被支气管败血波氏杆菌感染会诱导多种细胞因子/趋化因子的分泌，以调节气道炎症。其中，IL-1β和IL-6的分泌和表达呈剂量依赖性增加。有趣的是，在支气管败血波氏杆菌感染的PT-K75细胞中，通过Muc1基因表达产生的膜结合粘蛋白增加。然而，用特定的支气管败血波氏杆菌噬菌体（Bor-BRP-1）处理可显著抑制细胞因子产生和Muc1基因表达。支气管败血波氏杆菌噬菌体对支气管败血波氏杆菌诱导炎症中细胞因子谱的调节对于避免不适当的炎症反应至关重要。噬菌体通过抑制细菌感染来下调免疫反应的能力强调了基于噬菌体的疗法作为猪呼吸道新型抗炎治疗策略的可能性。
