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COVID-19 Patients Upregulate Toll-like Receptor 4-mediated Inflammatory Signaling That Mimics Bacterial Sepsis

Journal of Korean Medical Science 2020년 35권 38호 p.343 ~ 343
손경목, 이성권, 김현지, 천신혜, 정형석, 이주연, 김인수, Silwal Prashanta, 김영재, 백승화, 정재욱, 박춘구, 김연숙, 조은경,
소속 상세정보
손경목 ( Sohn Kyung-Mok ) - Chungnam National University School of Medicine Department of Internal Medicine
이성권 ( Lee Sung-Gwon ) - Chonnam National University School of Biological Sciences and Technology
김현지 ( Kim Hyeon-Ji ) - Chonnam National University School of Biological Sciences and Technology
천신혜 ( Cheon Shin-Hyea ) - Chungnam National University School of Medicine Department of Internal Medicine
정형석 ( Jeong Hyeong-Seok ) - Chungnam National University School of Medicine Department of Internal Medicine
이주연 ( Lee Joo-Yeon ) - Chungnam National University School of Medicine Department of Internal Medicine
김인수 ( Kim In-Soo ) - Chungnam National University School of Medicine Department of Microbiology
 ( Silwal Prashanta ) - Chungnam National University School of Medicine Department of Microbiology
김영재 ( Kim Young-Jae ) - Chungnam National University School of Medicine Department of Microbiology
백승화 ( Paik Seung-Wha ) - Chungnam National University School of Medicine Department of Microbiology
정재욱 ( Chung Chae-Uk ) - Chungnam National University School of Medicine Department of Internal Medicine
박춘구 ( Park Chun-Goo ) - Chonnam National University School of Biological Sciences and Technology
김연숙 ( Kim Yeon-Sook ) - Chungnam National University School of Medicine Department of Internal Medicine
조은경 ( Jo Eun-Kyeong ) - Chungnam National University School of Medicine Department of Microbiology

Abstract


Background: Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a ‘cytokine storm’ is involved in the pathogenesis of severe illness. However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls (HC).

Methods: A total of 48 subjects including 28 COVID-19 patients (8 severe/critical vs. 20 mild/moderate cases) admitted to Chungnam National University Hospital, and age/sex-matched 20 HC were enrolled in this study. PBMCs from the subjects were processed for nCounter Human Immunology gene expression assay to analyze the immune related transcriptome profiles. Recombinant proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were used to stimulate the PBMCs and monocyte-derived macrophages, and real-time polymerase chain reaction was performed to quantify the mRNA expressions of the pro-inflammatory cytokines/chemokines.

Results: Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. We also observed that recombinant S2 and nucleocapsid proteins of SARS-CoV-2 significantly increased pro-inflammatory cytokines/chemokines and S100A9 in human primary PBMCs.

Conclusion: These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.

키워드

SARS-CoV-2; Inflammation; Cytokines; S100A9

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