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  3. Metabolomic profiling of parapneumonic effusion reveals a regulatory role of dipeptides in interleukin-8 production in neutrophil-like cells

Metabolomic profiling of parapneumonic effusion reveals a regulatory role of dipeptides in interleukin-8 production in neutrophil-like cells

  • Anal Chim Acta. 2020 Sep 1;1128:238-250. doi: 10.1016/j.aca.2020.06.022.
Pei-Chun Hsueh 1,  Kuo-An Wu 2,  Chia-Yu Yang 3,  Chia-Wei Hsu 4,  Chih-Liang Wang 5,  Chu-Mi Hung 6,  Yi-Ting Chen 7,  Jau-Song Yu 8,  Chih-Ching Wu 9
Affiliations

Affiliations

  • 1 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 2 Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
  • 3 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 4 Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • 5 Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
  • 6 Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 7 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • 8 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
  • 9 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: [email protected].
PMID: 32825908 DOI: 10.1016/j.aca.2020.06.022
Abstract

Bacterial pneumonia is a lethal condition, and approximately 40% of Bacterial pneumonia patients experience parapneumonic effusion (PPE). Based on the severity of inflammation, PPEs can be categorized as early-stage uncomplicated PPE (UPPE), advanced-stage complicated PPE (CPPE) and, most seriously, thoracic empyema. Appropriate Antibiotic treatment at the early stage of PPE can prevent PPE progression and reduce mortality, indicating that understanding PPE generation and components can help researchers develop corresponding treatment strategies for PPE. To this end, metabolomes of 73 PPE (38 UPPE and 35 CPPE samples) and 30 malignant pleural effusion (MPE) samples were profiled with differential 12C2-/13C2-isotope dansylation labeling-based mass spectrometry. We found that PPE is characterized by elevated levels of dipeptides, especially for PPEs at advanced stages. Furthermore, with integrated proteomic and transcriptomic analyses of PPEs, the levels of dipeptides were strongly associated with the production of interleukin-8 (IL-8), an inflammation-associated cytokine. The production of IL-8 indeed increased upon the treatment of HL-60-derived neutrophilic cells with dipeptides, Gly-Val and Gly-Tyr. Our findings help to elucidate the metabolic perturbations present in PPE and indicate for the first time that dipeptides may be involved in the immune regulation observed during PPE progression.

Keywords

Dipeptides; Interleukin-8; Mass spectrometry; Metabolomics; Neutrophil; Parapneumonic effusion.

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