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World J Clin Cases. Mar 6, 2021; 9(7): 1513-1523
Published online Mar 6, 2021. doi: 10.12998/wjcc.v9.i7.1513
Regulation of the expression of proinflammatory cytokines induced by SARS-CoV-2
Xiang-Ning Zhang, Long-Ji Wu, Xia Kong, Bi-Ying Zheng, Zhe Zhang, Zhi-Wei He
Xiang-Ning Zhang, Long-Ji Wu, Xia Kong, Zhi-Wei He, Department of Pathophysiology, Guangdong Medical University, Dongguan 523808, Guangdong Province, China
Bi-Ying Zheng, Department of Clinical Microbiology, Institute of Laboratory Medicine, Guangdong Medical University, Dongguan 523808, Guangdong Province, China
Zhe Zhang, Department of ENT and Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 531000, Guangxi Zhuang Autonomous Region, China
Author contributions: Zhang XN, Zhang Z and He ZW conceived and designed the study; Zhang XN, Wu LJ and Kong X wrote the paper; Zhang XN, Zheng BY and He ZW corrected the paper.
Supported by Medical Scientific Research Foundation of Guangdong Province of China, Guangdong Provincial Health Commission, China, No. A2018356.
Conflict-of-interest statement: I hereby declare that the corresponding author of the submitted manuscript is supported by a research grant from the Medical Scientific Research Foundation of Guangdong Province of China during the preparation of the paper; the funding agency has no influence on the preparation on the present manuscript; but the conceived idea of the paper was inspired by the supported research.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiang-Ning Zhang, MD, PhD, Associate Professor, Department of Pathophysiology, Guangdong Medical University, No. 1 Xincheng Road, Songshan Lake District, Dongguan 523808, Guangdong Province, China. zhangxn_2006@126.com
Received: October 13, 2020
Peer-review started: October 13, 2020
First decision: November 26, 2020
Revised: December 8, 2020
Accepted: December 24, 2020
Article in press: December 24, 2020
Published online: March 6, 2021
Processing time: 138 Days and 14.5 Hours
Abstract

An outbreak of a novel coronavirus was reported in Wuhan, China, in late 2019. It has spread rapidly through China and many other countries, causing a global pandemic. Since February 2020, over 28 countries/regions have reported confirmed cases. Individuals with the infection known as coronavirus disease-19 (COVID-19) have similar clinical features as severe acute respiratory syndrome first encountered 17 years ago, with fever, cough, and upper airway congestion, along with high production of proinflammatory cytokines (PICs), which form a cytokine storm. PICs induced by COVID-19 include interleukin (IL)-6, IL-17, and monocyte chemoattractant protein-1. The production of cytokines is regulated by activated nuclear factor-kB and involves downstream pathways such as Janus kinase/signal transducers and activators transcription. Protein expression is also regulated by post-translational modification of chromosomal markers. Lysine residues in the peptide tails stretching out from the core of histones bind the sequence upstream of the coding portion of genomic DNA. Covalent modification, particularly methylation, activates or represses gene transcription. PICs have been reported to be induced by histone modification and stimulate exudation of hyaluronic acid, which is implicated in the occurrence of COVID-19. These findings indicate the impact of the expression of PICs on the pathogenesis and therapeutic targeting of COVID-19.

Keywords: SARS-CoV-2; COVID-19; Proinflammatory cytokines; Transcription factor; Histone; Post-translational modification

Core Tip: An infection by a novel coronavirus which originated in Wuhan, China has spread rapidly, causing a global pandemic. Clinically the infection known as coronavirus disease-19 (COVID-19) is similar to severe acute respiratory syndrome, with fever, cough, and upper airway congestion, along with high production of proinflammatory cytokines (PICs), forming a cytokine storm. PICs induced include interleukin (IL)-6, IL-17, and monocyte chemoattractant protein-1. Their production is regulated by transcription factors, and post-translational modification of histones, which activates or represses gene transcription. PICs in turn stimulate exudation of hyaluronic acid, implicated in the pathogenesis of COVID-19. Their role as therapeutic targets is suggested.