» Articles » PMID: 33553423

Overexpression of Limb Bud and Heart Alleviates Sepsis-Induced Acute Lung Injury Via Inhibiting the NLRP3 Inflammasome

Overview
Journal Biomed Res Int
Publisher Wiley
Date 2021 Feb 8
PMID 33553423
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Objective: Sepsis is a leading cause of acute lung injury (ALI). This study attempted to investigate the effects of limb bud and heart (LBH) on the development of sepsis-induced ALI and its underlying mechanism of action.

Methods: The sepsis-induced ALI mouse model was established by cecal ligation and puncture (CLP). The lung injury score and lung wet/dry weight (W/D) ratio were used to evaluate the lung injury. , ALI was simulated by lipopolysaccharide (LPS) treatment in A549 cells. The mRNA expression of LBH, NLRP3, ASC, and proinflammatory cytokines was measured by qRT-PCR. The viability of LPS-induced A549 cells was analyzed by MTT assay. Furthermore, western blot was performed to detect the protein expression of LBH, NLRP3, and ASC. LPS-induced A549 cells were treated with MCC950 (NLRP3 inflammasome inhibitor) to confirm the effect of LBH on NLRP3 inflammasome.

Results: The mRNA and protein expression of LBH was decreased in sepsis-induced ALI. LBH overexpression reduced the lung injury score, lung W/D ratio, expression of proinflammatory cytokines, and NLRP3 inflammasome activation in sepsis-induced ALI mouse model. Additionally, LBH upregulation increased the viability, while it decreased the proinflammatory cytokine expression and NLRP3 inflammasome activation of LPS-induced A549 cells. Moreover, MCC950 reversed the promoting effects of LBH silencing on proinflammatory cytokine expression and NLRP3 inflammasome activation in LPS-induced A549 cells.

Conclusions: LBH alleviated lung injury in sepsis-induced ALI mouse model by inhibiting inflammation and NLRP3 inflammasome, and restrained the inflammation by inhibiting NLRP3 inflammasome in LPS-induced A549 cells, providing a novel therapeutic target for ALI.

Citing Articles

Glycyrrhizic Acid Protects Experimental Sepsis Rats against Acute Lung Injury and Inflammation.

Shen J, Hua Z, Chai Y Evid Based Complement Alternat Med. 2022; 2022:3571800.

PMID: 36072408 PMC: 9444394. DOI: 10.1155/2022/3571800.


Terretonin as a New Protective Agent against Sepsis-Induced Acute Lung Injury: Impact on SIRT1/Nrf2/NF-κBp65/NLRP3 Signaling.

Mohamed G, Ibrahim S, El-Agamy D, Elsaed W, Sirwi A, Asfour H Biology (Basel). 2021; 10(11).

PMID: 34827212 PMC: 8614783. DOI: 10.3390/biology10111219.

References
1.
Fujishima S, Gando S, Daizoh S, Kushimoto S, Ogura H, Mayumi T . Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock. Respirology. 2016; 21(5):898-904. DOI: 10.1111/resp.12769. View

2.
Liu Q, Guan X, Lv J, Li X, Wang Y, Li L . Limb-bud and Heart (LBH) functions as a tumor suppressor of nasopharyngeal carcinoma by inducing G1/S cell cycle arrest. Sci Rep. 2015; 5:7626. PMC: 4283826. DOI: 10.1038/srep07626. View

3.
Gong J, Wu Z, Qi H, Chen L, Li H, Li B . Maresin 1 mitigates LPS-induced acute lung injury in mice. Br J Pharmacol. 2014; 171(14):3539-50. PMC: 4105939. DOI: 10.1111/bph.12714. View

4.
He Y, Hara H, Nunez G . Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends Biochem Sci. 2016; 41(12):1012-1021. PMC: 5123939. DOI: 10.1016/j.tibs.2016.09.002. View

5.
Chang Y, Sheng Y, Cheng Y, Lin Y, Zhu Z, Wen L . Downregulated expression of LBH mRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. J Dermatol. 2015; 43(1):99-102. DOI: 10.1111/1346-8138.13006. View