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Carvedilol alleviates lipopolysaccharide (LPS)-induced acute lung injury by inhibiting Ras homolog family member A (RhoA)/ROCK activities - PubMed

Carvedilol alleviates lipopolysaccharide (LPS)-induced acute lung injury by inhibiting Ras homolog family member A (RhoA)/ROCK activities

Jing Xu et al. Bioengineered. 2022 Feb.

Abstract

Carvedilol possess multiple functions such as antioxidation and neuroprotection RhoA/ROCK is reported to participate in acute lung injury (ALI). The aim of the present study was to explore the role of carvedilol in LPS-induced ALI. BEAS2B cells were subjected to LPS for the construction of in vitro ALI model. After that, the protective effects of carvedilol were evaluated by Cell Counting Kit-8 (CCK-8). The activities of RhoA/ROCK were then measured to confirm its association with carvedilol by quantitative reverse transcription PCR (RT-qPCR) and Western blot. Then, the cell viability, inflammatory responses, oxidative stress and apoptosis were detected by CCK-8, enzyme linked immunosorbent assay (ELISA), oxidative stress detection kits, and TdT-mediated dUTP Nick-End Labeling (TUNEL) respectively. Inflammation- and apoptosis-related markers were also measured by Western blot. The cell viability reduced by LPS in BEAS2B cells was elevated by carvedilol. Moreover, RhoA/ROCK were found to be suppressed by carvedilol administration. The cell viability, inflammation, oxidative stress and apoptosis of LPS-induced BEAS2B cells were aggravated upon RhoA was overexpressed. Collectively, carvedilol exerts a protective effect against LPS-induced injury that could be ascribed to its anti-inflammatory and antioxidative character through modulating the RhoA/ROCK activities.

Keywords: Carvedilol; Rhoa/ROCK; acute lung injury.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.

The effect of carvedilol on cell viability of LPS-induced BEAS2B cells. (a) The cell viability of BEAS2B cells treated with carvedilol. (b) The cell viability of LPS-induced BEAS2B cells treated with carvedilol. ***P < 0.001 Versus Control, ###P < 0.001 Versus LPS.

Figure 2.
Figure 2.

Carvedilol reduces the expression of RhoA and ROCK in LPS-induced BEAS2B cells. (a-b) The expression of RhoA in LPS-induced BEAS2B cells. (c) The expression of MYPT1 in LPS-induced BEAS2B cells. ***P < 0.001 Versus Control, ###P < 0.001 Versus LPS.

Figure 3.
Figure 3.

Carvedilol reduces the cell viability, inflammation and oxidative stress of LPS-induced BEAS2B cells by inhibiting RhoA/ROCK activities. (a-b) The expression of RhoA after the plasmid overexpressing RhoA was constructed. ***P < 0.001 Versus Ov-NC. (c) The cell viability of LPS-induced BEAS2B cells transfected with Ov-RhoA. (d) The expression of inflammatory cytokines in LPS-induced BEAS2B cells transfected with Ov-RhoA, detected by ELISA. (e) The expression of inflammation-related markers in LPS-induced BEAS2B cells transfected with Ov-RhoA, detected by Western blot. (f) The levels of ROS, MDA, and SOD in LPS-induced BEAS2B cells transfected with Ov-RhoA *P < 0.05, ***P < 0.001 Versus LPS. ###P < 0.001 Versus LPS+5 µM+Ov-NC.

Figure 4.
Figure 4.

Carvedilol reduces apoptosis of LPS-induced BEAS2B cells by inhibiting RhoA/ROCK activities. (a-b) The apoptosis of LPS-induced BEAS2B cells transfected with Ov-RhoA. ***P < 0.001 Versus LPS. ###P < 0.001 Versus LPS+5 µM+Ov-NC.

Figure5.
Figure5.

Carvedilol affects the expression levels of apoptosis-related proteins in LPS-induced BEAS2B cells by inhibiting RhoA/ROCK activities. The expression of apoptosis-related proteins, including Bax, Bad, cleaved caspase3 and Bcl-2 in LPS-induced BEAS2B cells transfected with Ov-RhoA. ***P < 0.001 Versus LPS. ##P < 0.01, ###P < 0.001 Versus LPS+5 µM+Ov-NC.

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References

    1. Li Y, Huang J, Foley NM, et al. B7H3 ameliorates LPS-induced acute lung injury via attenuation of neutrophil migration and infiltration. Sci Rep. 2016;6(1):31284. - PMC - PubMed
    1. Lederer PA, Zhou T, Chen W, et al. Mathew B and Jacobson JR. Attenuation of murine acute lung injury by PF-573,228, an inhibitor of focal adhesion kinase. Vascul Pharmacol. 2018;110:16–23. - PMC - PubMed
    1. Kallet RH, Lipnick MS, Pirracchio R.. Acute Respiratory Distress Syndrome Outcomes in Non-Research Subjects Assessed by Generalized Prospective Trial Eligibility Criteria and Adherance to Lung-Protective Ventilation. Respir Care. 2021;66(9):1380–1388. - PubMed
    1. Krupa A, Fol M, Rahman M, et al. Rosenfield GR and Kurdowska AK. Silencing Bruton’s tyrosine kinase in alveolar neutrophils protects mice from LPS/immune complex-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2014;307(6):L435–448. - PMC - PubMed
    1. Zhang QL, Yang JJ, Zhang HS. Carvedilol (CAR) combined with carnosic acid (CAA) attenuates doxorubicin-induced cardiotoxicity by suppressing excessive oxidative stress, inflammation, apoptosis and autophagy. Biomed Pharmacother. 2019;109:71–83. - PubMed

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