North Carolina Jaycee Burn Center, Department of Surgery, Chapel Hill, NC 27514, USA.
Division of Oral and Craniofacial Health Sciences Adams School of Dentistry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Int J Mol Sci. 2022 Aug 20;23(16):9418. doi: 10.3390/ijms23169418.
Burn patients are subject to significant acute immune and metabolic dysfunction. Concomitant inhalation injury increases mortality by 20%. In order to identify specific immune and metabolic signaling pathways in burn (B), inhalation (I), and combined burn-inhalation (BI) injury, unbiased nanoString multiplex technology was used to investigate gene expression within peripheral blood mononuclear cells (PBMCs) from burn patients, with and without inhalation injury. PBMCs were collected from 36 injured patients and 12 healthy, non-burned controls within 72 h of injury. mRNA was isolated and hybridized with probes for 1342 genes related to general immunology and cellular metabolism. From these specific gene patterns, specific cellular perturbations and signaling pathways were inferred using robust bioinformatic tools. In both B and BI injuries, elements of mTOR, PPARγ, TLR, and NF-kB signaling pathways were significantly altered within PBMC after injury compared to PBMC from the healthy control group. Using linear regression modeling, (1) DEPTOR, LAMTOR5, PPARγ, and RPTOR significantly correlated with patient BMI; (2) RPTOR significantly correlated with patient length of stay, and (3) MRC1 significantly correlated with the eventual risk of patient mortality. Identification of mediators of this immunometabolic response that can act as biomarkers and/or therapeutic targets could ultimately aid the management of burn patients.
烧伤患者会出现明显的急性免疫和代谢功能障碍。同时合并吸入性损伤会使死亡率增加 20%。为了明确烧伤（B）、吸入性损伤（I）和合并烧伤吸入性损伤（BI）患者外周血单个核细胞（PBMC）中特定的免疫和代谢信号通路，本研究采用无偏性的纳升串联质谱技术，检测了合并或不合并吸入性损伤的烧伤患者 PBMC 中的基因表达。在损伤后 72 小时内，采集了 36 名烧伤患者和 12 名健康、非烧伤对照者的 PBMC。提取 mRNA 后，用针对与一般免疫学和细胞代谢相关的 1342 个基因的探针进行杂交。通过这些特定的基因图谱，使用强大的生物信息学工具推断出特定的细胞扰动和信号通路。与健康对照组相比，在 BI 和 B 损伤后，PBMC 中的 mTOR、PPARγ、TLR 和 NF-kB 信号通路的相关基因表达发生了显著改变。通过线性回归模型，（1）DEPTOR、LAMTOR5、PPARγ 和 RPTOR 与患者 BMI 显著相关；（2）RPTOR 与患者住院时间显著相关；（3）MRC1 与患者死亡风险显著相关。鉴定出这些免疫代谢反应的介质，这些介质可作为生物标志物和/或治疗靶点，最终可能有助于烧伤患者的管理。
