Open Access

Lipoxin A4 protects against paraquat‑induced acute lung injury by inhibiting the TLR4/MyD88‑mediated activation of the NF‑κB and PI3K/AKT pathways

  • Authors:
    • Yuhua Li
    • Na Wang
    • Zhongliang Ma
    • Yunwen Wang
    • Yuan Yuan
    • Zhitao Zhong
    • Yi Hong
    • Min Zhao
  • View Affiliations

  • Published online on: March 19, 2021     https://doi.org/10.3892/ijmm.2021.4919
  • Article Number: 86
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Paraquat (PQ) causes serious oxidative stress and inflammatory responses, particularly to the lungs. Since lipoxin A4 (LXA4) functions as an anti‑inflammatory mediator, the present study aimed to explore its effects on PQ‑induced acute lung injury (ALI) and to elucidate the possible underlying mechanisms. PQ was administered to male SD rats and RAW264.7 cells to establish a model of poisoning, and LXA4 was used as an intervention drug. LXA4 treatment attenuated PQ‑induced lung injury, and this was accompanied by decreased tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β secretion levels, and reduced oxidative stress damage. Additionally, LXA4 treatment inhibited the activation of the inflammation‑related signaling molecules, Toll‑like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor (NF)‑κB p65, p‑phosphoinositide 3‑kinase (PI3K) and p‑AKT. Furthermore, the in vitro experiments further confirmed that the beneficial effects of LXA4 on PQ‑induced damage were TLR4‑dependent. Hence, the present study demonstrated that LXA4 attenuated PQ‑induced toxicity in lung tissue and RAW264.7 macrophages, and that this protective effect may be closely related to the mitigation of inflammatory responses, oxidative stress damage and the TLR4/MyD88‑mediated activation of the PI3K/AKT/NF‑κB pathway.
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May-2021
Volume 47 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Li Y, Wang N, Ma Z, Wang Y, Yuan Y, Zhong Z, Hong Y and Zhao M: Lipoxin A4 protects against paraquat‑induced acute lung injury by inhibiting the TLR4/MyD88‑mediated activation of the NF‑κB and PI3K/AKT pathways. Int J Mol Med 47: 86, 2021.
APA
Li, Y., Wang, N., Ma, Z., Wang, Y., Yuan, Y., Zhong, Z. ... Zhao, M. (2021). Lipoxin A4 protects against paraquat‑induced acute lung injury by inhibiting the TLR4/MyD88‑mediated activation of the NF‑κB and PI3K/AKT pathways. International Journal of Molecular Medicine, 47, 86. https://doi.org/10.3892/ijmm.2021.4919
MLA
Li, Y., Wang, N., Ma, Z., Wang, Y., Yuan, Y., Zhong, Z., Hong, Y., Zhao, M."Lipoxin A4 protects against paraquat‑induced acute lung injury by inhibiting the TLR4/MyD88‑mediated activation of the NF‑κB and PI3K/AKT pathways". International Journal of Molecular Medicine 47.5 (2021): 86.
Chicago
Li, Y., Wang, N., Ma, Z., Wang, Y., Yuan, Y., Zhong, Z., Hong, Y., Zhao, M."Lipoxin A4 protects against paraquat‑induced acute lung injury by inhibiting the TLR4/MyD88‑mediated activation of the NF‑κB and PI3K/AKT pathways". International Journal of Molecular Medicine 47, no. 5 (2021): 86. https://doi.org/10.3892/ijmm.2021.4919