Affiliation:
1. Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
Abstract
Background and Objective:
Hydroxychloroquine (HCQ) is a molecule derived from
quinacrine; it displays a wide range of pharmacological properties, including anti-inflammatory,
immunomodulatory, and antineoplastic. However, little is known about this molecule’s role in
lung injury. This study aimed to identify HCQ’s regulatory role of HCQ in sepsis-induced lung injury
and its molecular mechanism. Methods: To test the protective properties of HCQ, we established
an in vivo model of lipopolysaccharide (LPS)-induced lung injury in mice. The extent of the
injury was determined by evaluating histopathology, inflammatory response, oxidative stress, and
apoptosis. Mechanistically, conventional nucleotide-binding oligomerization domain leucine-rich
repeat and pyrin domain-containing 3 (NLRP3) knockout mice were employed to investigate
whether HCQ exerted pulmonary protection by inhibiting NLRP3-mediated pyroptosis.
Results:
Our findings revealed that HCQ pretreatment significantly mitigated LPS-induced lung
injury in mice in terms of histopathology, inflammatory response, oxidative stress, and apoptosis,
while inhibiting LPS-induced NLRP3 inflammasome activation and pyroptosis. Additionally, the
indicators of lung injury, including histopathology, inflammatory response, oxidative stress, and
apoptosis, were still reduced drastically in LPS-treated NLRP3 (-/-) mice after HCQ pretreatment.
Notably, HCQ pretreatment further decreased the levels of pyroptosis indicators, including IL-1β,
IL-18 and Cle-GSDMD, in LPS-treated NLRP3 (-/-) mice.
Conclusion:
Taken together, HCQ protects against lung injury by inhibiting pyroptosis, maybe not
only through the NLRP3 pathway but also through non-NLRP3 pathway; therefore, it may be a
new therapeutic strategy in the treatment of lung injury.
Funder
National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
General Health Professions