Khanh Hoang Nguyen, Maegawa Eiji, Murakami Shigeru, Schaffer Stephen W, Ito Takashi
Faculty of Bioscience and Biotechnology, Fukui Prefectural University, Eiheiji 910-1195, Japan.
Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
Metabolites. 2022 Apr 14;12(4):349. doi: 10.3390/metabo12040349.
Lung infection can evoke pulmonary and systemic inflammation, which is associated with systemic severe symptoms, such as skeletal muscle wasting. While -chlorotaurine (also known as taurine chloramine; TauCl) has anti-inflammatory effects in cells, its effects against pulmonary and systemic inflammation after lung infection has not been elucidated. In the present study, we evaluated the anti-inflammatory effect of the taurine derivative, TauCl against -derived lipopolysaccharide (LPS)-induced pneumonia in obese mice maintained on a high fat diet. In this study, TauCl was injected intraperitoneally 1 h before intratracheal LPS administration. While body weight was decreased by 7.5% after LPS administration, TauCl treatment suppressed body weight loss. TauCl also attenuated the increase in lung weight due to lung edema. While LPS-induced acute pneumonia caused an increase in cytokine/chemokine mRNA expression, including that of IL-1β, -6, TNF-α, MCP-1, TauCl treatment attenuated IL-6, and TNF-alpha expression, but not IL-1β and MCP-1. TauCl treatment partly attenuated the elevation of the serum cytokines. Furthermore, TauCl treatment alleviated skeletal muscle wasting. Importantly, LPS-induced expression of Atrogin-1, MuRF1 and IκB, direct or indirect targets for NFκB, were suppressed by TauCl treatment. These findings suggest that intraperitoneal TauCl treatment attenuates acute pneumonia-related pulmonary and systemic inflammation, including muscle wasting, in vivo.
肺部感染可引发肺部和全身性炎症,这与全身性严重症状相关,如骨骼肌萎缩。尽管氯代牛磺酸(也称为牛磺酸氯胺;TauCl)在细胞中具有抗炎作用,但其对肺部感染后肺部和全身性炎症的影响尚未阐明。在本研究中,我们评估了牛磺酸衍生物TauCl对高脂饮食喂养的肥胖小鼠中脂多糖(LPS)诱导的肺炎的抗炎作用。在本研究中,在气管内给予LPS前1小时腹腔注射TauCl。LPS给药后体重下降了7.5%,而TauCl治疗可抑制体重减轻。TauCl还减轻了因肺水肿导致的肺重量增加。虽然LPS诱导的急性肺炎导致细胞因子/趋化因子mRNA表达增加,包括IL-1β、-6、TNF-α、MCP-1,但TauCl治疗可减轻IL-6和TNF-α的表达,但对IL-1β和MCP-1无影响。TauCl治疗部分减轻了血清细胞因子的升高。此外,TauCl治疗减轻了骨骼肌萎缩。重要的是,TauCl治疗可抑制LPS诱导的Atrogin-1、MuRF1和IκB的表达,它们是NFκB的直接或间接靶点。这些发现表明,腹腔注射TauCl治疗可减轻体内急性肺炎相关的肺部和全身性炎症,包括肌肉萎缩。