Open Access

Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells

  • Authors:
    • Jun Chang
    • Wei Zhang
  • View Affiliations

  • Published online on: December 30, 2022     https://doi.org/10.3892/etm.2022.11778
  • Article Number: 79
  • Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Remifentanil is a widely used in general anesthetic that has been found to suppress the inflammatory response in aortic endothelial cells. Therefore, it was hypothesized that remifentanil can inhibit inflammatory dysfunction in lung epithelial cells to alleviate acute lung injury (ALI). The present study aimed to examine the effects of remifentanil on inflammatory injury, MMP‑9/tissue inhibitor of metalloproteinase 1 (TIMP1) balance and the potential associated regulatory pathways in A549 cells. Lipopolysaccharide (LPS) was used to treat A549 cells to establish ALI models. The possible roles of different concentrations of remifentanil in cell viability was then determined by CCK‑8 and Lactate dehydrogenase release assay. Apoptosis was assessed by flow cytometry analysis and western blotting. Inflammation and oxidative stress were measured by ELISA and corresponding kits respectively. Subsequently, the effects of remifentanil on Toll‑like receptor 4 (TLR4) expression and the MMP‑9/TIMP1 balance were assessed by western blotting and ELISA. In addition, the effects of remifentanil on NF‑κB/STAT3 signaling were evaluated by measuring the protein expression levels of associated pathway components and the degree of NF‑κB nuclear translocation using western blotting and immunofluorescence respectively. Remifentanil was found to increase cell viability whilst reducing apoptosis, inflammation and oxidative stress in the LPS‑treated cells. In addition, TLR4 inhibitor CLI‑095 suppressed MMP‑9 expression and secretion while potentiating TIMP1 expression and secretion in LPS‑challenged cells. Remifentanil treatment was able to modulate TLR4 to mediate LPS‑induced MMP‑9/TIMP1 imbalance and suppress the phosphorylation of NF‑κB/STAT3 signaling components, in addition to inhibiting NF‑κB nuclear translocation. Taken together, remifentanil downregulated TLR4 to reduce MMP‑9/TIMP1 imbalance to inhibit inflammatory dysfunction in LPS‑treated A549 cells, by regulating NF‑κB/STAT3 signaling.
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February-2023
Volume 25 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Chang J and Chang J: Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells. Exp Ther Med 25: 79, 2023
APA
Chang, J., & Chang, J. (2023). Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells. Experimental and Therapeutic Medicine, 25, 79. https://doi.org/10.3892/etm.2022.11778
MLA
Chang, J., Zhang, W."Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells". Experimental and Therapeutic Medicine 25.2 (2023): 79.
Chicago
Chang, J., Zhang, W."Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells". Experimental and Therapeutic Medicine 25, no. 2 (2023): 79. https://doi.org/10.3892/etm.2022.11778