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基因表达可预测小鼠中诱导性脓毒性关节炎。

Gene expression of predicts -induced septic arthritis in mice.

作者信息

Deshmukh Meghshree, Subhash Santhilal, Hu Zhicheng, Mohammad Majd, Jarneborn Anders, Pullerits Rille, Jin Tao, Kopparapu Pradeep Kumar

机构信息

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States.

出版信息

Front Microbiol. 2023 Jun 15;14:1146694. doi: 10.3389/fmicb.2023.1146694. eCollection 2023.

Abstract

Septic arthritis is the most aggressive joint disease associated with high morbidity and mortality. The interplay of the host immune system with the invading pathogens impacts the pathophysiology of septic arthritis. Early antibiotic treatment is crucial for a better prognosis to save the patients from severe bone damage and later joint dysfunction. To date, there are no specific predictive biomarkers for septic arthritis. Transcriptome sequencing analysis identified genes to be highly expressed in septic arthritis compared to non-septic arthritis at the early course of infection in an septic arthritis mouse model. Importantly, downregulation of mRNA expression at the early course of infection was noticed in mice infected with the Sortase A/B mutant strain totally lacking arthritogenic capacity compared with the mice infected with parental arthritogenic strain. The mice infected intra-articularly with the arthritogenic strain significantly increased protein expression levels in joints over time. Intriguingly, the synthetic bacterial lipopeptide Pam2CSK4 was more potent than Pam3CSK4 in inducing release upon intra-articular injection of these lipopeptides into the mouse knee joints. Such an effect was dependent on the presence of monocytes/macrophages. In conclusion, gene expression may serve as a potential biomarker to predict septic arthritis, enabling the development of more effective treatment strategies.

摘要

脓毒性关节炎是最具侵袭性的关节疾病,与高发病率和死亡率相关。宿主免疫系统与入侵病原体之间的相互作用影响脓毒性关节炎的病理生理学。早期抗生素治疗对于获得更好的预后至关重要,可使患者免于严重的骨损伤和后期的关节功能障碍。迄今为止,尚无脓毒性关节炎的特异性预测生物标志物。转录组测序分析发现在脓毒性关节炎小鼠模型感染早期,与非脓毒性关节炎相比,某些基因在脓毒性关节炎中高表达。重要的是,与感染亲本致关节炎菌株的小鼠相比,感染完全缺乏致关节炎能力的分选酶A/B突变株的小鼠在感染早期mRNA表达下调。关节内注射致关节炎菌株的小鼠关节中蛋白质表达水平随时间显著增加。有趣的是,合成细菌脂肽Pam2CSK4在将这些脂肽关节内注射到小鼠膝关节时比Pam3CSK4更有效地诱导释放。这种效应依赖于单核细胞/巨噬细胞的存在。总之,基因表达可能作为预测脓毒性关节炎的潜在生物标志物,从而有助于开发更有效的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf48/10307981/193907120583/fmicb-14-1146694-g001.jpg

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