デグチ　アツコ   DEGUCHI Atsuko   出口　敦子    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	S100A8 may govern hyper-inflammation in severe COVID-19.
掲載誌名	正式名：FASEB journal 略　 称：FASEB J ISSNコード：15306860/08926638
掲載区分	国外
巻・号・頁	35(9),pp.e21798
著者・共著者	Deguchi Atsuko, Yamamoto Tomoko, Shibata Noriyuki, Maru Yoshiro
担当区分	筆頭著者
発行年月	2021/09
概要	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