出口　敦子
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Professor
Article types Original article
Language English
Peer review Non peer reviewed
Title S100A8 may govern hyper-inflammation in severe COVID-19.
Journal Formal name：FASEB journal
Abbreviation：FASEB J
ISSN code：15306860/08926638
Domestic / ForeginForegin
Volume, Issue, Page 35(9),pp.e21798
Author and coauthor Deguchi Atsuko, Yamamoto Tomoko, Shibata Noriyuki, Maru Yoshiro
Authorship Lead author
Publication date 2021/09
Summary The coronavirus disease 2019 (COVID-19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID-19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. The most successful analogy is found in BCR-ABL in chronic myeloid leukemia, which is the golden biomarker, and simultaneously, the most effective molecular target. We hypothesize that S100 calcium-binding protein A8 (S100A8) is one such molecule. The underlying evidence includes accumulating clinical information that S100A8 is upregulated in severe forms of COVID-19, pathological similarities of the affected lungs between COVID-19 and S100A8-induced acute respiratory distress syndrome (ARDS) model, homeostatic inflammation theory in which S100A8 is an endogenous ligand for endotoxin sensor Toll-like receptor 4/Myeloid differentiation protein-2 (TLR4/MD-2) and mediates hyper-inflammation even after elimination of endotoxin-producing extrinsic pathogens, analogous findings between COVID-19-associated ARDS and pre-metastatic lungs such as S100A8 upregulation, pulmonary recruitment of myeloid cells, increased vascular permeability, and activation coagulation cascade. A successful treatment in an animal COVID-19 model is given with a reagent capable of abrogating interaction between S100A8/S100A9 and TLR4. In this paper, we try to verify our hypothesis that S100A8 governs COVID-19-associated ARDS.
DOI 10.1096/fj.202101013
PMID 34339064