SerpinB1 is required for Rev-erbα-mediated protection against acute lung injury induced by lipopolysaccharide-in mice.

Autor: Xiao X; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Chen S; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Huang Z; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Han X; Department of Anesthesiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China., Dou C; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Kang J; Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Wang T; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Xie H; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Zhang L; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Hei Z; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Li H; Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Yao W; Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2023 Dec; Vol. 180 (24), pp. 3234-3253. Date of Electronic Publication: 2023 Aug 28.
DOI: 10.1111/bph.16175
Abstrakt: Background and Purpose: Acute lung injury (ALI) is a serious, life-threatening inflammation of the lungs that still lacks effective treatment. We previously showed that serine protease inhibitor B1 (SerpinB1) protects against ALI induced by orthotopic autologous liver transplantation. However, the role of SerpinB1 in lipopolysaccharide (LPS)-induced ALI and its regulatory mechanisms are not known.
Experimental Approach: Wild-type (WT) and SerpinB1 knockout (KO) mice were treated with intratracheal LPS stimulation to induce ALI. Some of the WT and KO mice were injected i.p. with melatonin, a rhythm-related protein Rev-erbα agonist. The circadian rhythm in WT mice was disrupted by exposing mice to 24 h of continuous dark or light conditions after intratracheal LPS. Neutrophils were isolated from alveolar lavage fluid of WT and KO mice, and from human peripheral blood. Neutrophils were treated with LPS and melatonin.
Key Results: Disruption of circadian rhythm by either 24-h dark or light conditions exacerbated LPS-induced ALI and decreased expression of Rev-erbα and SerpinB1 protein in lung, whereas melatonin treatment increased SerpinB1 expression and attenuated LPS-induced ALI in WT mice, but not in KO mice. In isolated neutrophils, Rev-erbα was co-localized with SerpinB1 and bound to its promoter to trigger SerpinB1 transcription. Furthermore, LPS stimulation increased formation of neutrophil extracellular traps, which was reversed by melatonin treatment in neutrophils from WT mice, but not from KO mice.
Conclusion and Implications: In mice, SerpinB1 is rhythmically regulated by Rev-erbα, and its down-regulation exacerbates LPS-induced ALI by inducing formation of neutrophil extracellular traps.
(© 2023 British Pharmacological Society.)
Databáze: MEDLINE
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