Ectodomain Shedding May Play a Pivotal Role in Disease Severity in COVID-19

Rui Yamaguchi ,Yasuo Yamaguchi

doi:10.33696/signaling.2.040

Abstract

Ectodomain shedding mediated by a disintegrin and metalloprotease 10/17 (ADAM10/17) modulates the function of immune effector cells and may be involved in the novel coronavirus disease COVID-19. Toll-like receptor 7/8 (TLR7/8) recognizes single-strand RNA from viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) during the innate immune response, and TLR7/8 agonist activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate reactive oxygen species (ROS).

Highlights

Ectodomain shedding mediated by a disintegrin and metalloprotease 10/17 (ADAM10/17) modulates the function of immune effector cells and may be involved in the novel coronavirus disease COVID-19
ADAM10/7 was found to mediate ectodomain shedding to modulate immune responses [3] and to be activated by reactive oxygen species (ROS) [4]. These findings suggest that SARS-CoV-2 contributes to and induces ectodomain shedding, which may be associated with disease severity
In cells stimulated with interleukin-1β (IL-1β), the angiotensin II/angiotensin type 1 receptor (AT1) and AT2 axis augments expression of inducible nitric oxide synthase to generate nitric oxide (NO) [11]; NO reacts with the peroxidase domain of the enzyme dual oxidase 2, which has both a peroxidase domain and an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase domain, to produce the strong biological oxidant agent peroxynitrite (ONOO-)

Summary

Introduction

Ectodomain shedding mediated by a disintegrin and metalloprotease 10/17 (ADAM10/17) modulates the function of immune effector cells and may be involved in the novel coronavirus disease COVID-19. Toll-like receptor 7/8 (TLR7/8) recognizes single-strand RNA from viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19) during the innate immune response [1], and TLR7/8 agonist activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate reactive oxygen species (ROS) [2]. ADAM10/7 was found to mediate ectodomain shedding to modulate immune responses [3] and to be activated by ROS [4].

Results

Conclusion