Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury

Authors

Xiangyun Li
Nathanial K Berg
Tingting Mills
Kaiying Zhang
Holger K Eltzschig
Xiaoyi Yuan

Publication Date

1-1-2020

Journal

Frontiers in Immunology

Abstract

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine signaling to inhibit the inflammatory response in ARDS, while in chronic lung diseases, it promotes inflammation and tissue injury. In this review, we discuss the role of adenosine at the interphase of hypoxia and inflammation in ARDS and chronic lung diseases, as well as the current strategy for therapeutic targeting of the adenosine signaling pathway.

Keywords

Acute Lung Injury, Adenosine, Disease Management, Disease Susceptibility, Humans, Hypoxia, Hypoxia-Inducible Factor 1, Inflammation, Molecular Targeted Therapy, Receptors, Purinergic P1, Respiratory Distress Syndrome, Signal Transduction