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Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury

  • Authors:
    • Dandan Li
    • Weiying Ren
    • Zhilong Jiang
    • Lei Zhu
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    Affiliations: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Gerontology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4399-4409
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    Published online on: August 24, 2018
       https://doi.org/10.3892/mmr.2018.9427
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Abstract

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is characterized by uncontrolled progressive lung inflammation. Macrophages serve a key role in the pathogenesis of ALI/ARDS. Macrophage pyroptosis is a process of cell death releasing the proinflammatory cytokines interleukin (IL)‑1β and IL‑18. It was hypothesized that macrophage pyroptosis may partially account for the uncontrolled lung inflammation of ALI/ARDS. In the present study, greater macrophage pyroptosis in lipopolysaccharide (LPS)‑treated macrophages and the ALI/ARDS mouse model was observed. The expression of nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing (NLRP)3 and IL‑1β and cleavage of caspase‑1 were significantly elevated following LPS treatment accompanied by greater activation of p38 mitogen‑activated protein kinase (MAPK) signaling in vitro and in vivo. However, blocking p38 MAPK signaling through the inhibitor SB203580 significantly suppressed the acute lung injury and excessive lung inflammation in vivo, consistent with the reduced expression of the NLRP3 inflammasome and IL‑1β and cleavage of caspase‑1. Pretreatment of the rat NR8383 macrophage cell line with SB203580 significantly decreased the population of caspase‑1+PI+ pyroptotic cells and expression of NLRP3/IL‑1β. However, a larger population of Annexin V+PI‑ apoptotic cells was observed following blocking of the p38 MAPK signaling pathway. The results indicated that blockage of p38 MAPK signaling pathway skewed macrophage cell death from proinflammatory pyroptosis towards non‑inflammatory apoptosis. These effects may contribute to attenuated acute lung injury and excessive inflammation in the SB203580‑treated mice. The results may provide a novel therapeutic strategy for the treatment of uncontrolled lung inflammation in patients with ALI/ARDS.
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Copy and paste a formatted citation
Spandidos Publications style
Li D, Ren W, Jiang Z and Zhu L: Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Mol Med Rep 18: 4399-4409, 2018.
APA
Li, D., Ren, W., Jiang, Z., & Zhu, L. (2018). Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Molecular Medicine Reports, 18, 4399-4409. https://doi.org/10.3892/mmr.2018.9427
MLA
Li, D., Ren, W., Jiang, Z., Zhu, L."Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury". Molecular Medicine Reports 18.5 (2018): 4399-4409.
Chicago
Li, D., Ren, W., Jiang, Z., Zhu, L."Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury". Molecular Medicine Reports 18, no. 5 (2018): 4399-4409. https://doi.org/10.3892/mmr.2018.9427
Copy and paste a formatted citation
x
Spandidos Publications style
Li D, Ren W, Jiang Z and Zhu L: Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Mol Med Rep 18: 4399-4409, 2018.
APA
Li, D., Ren, W., Jiang, Z., & Zhu, L. (2018). Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Molecular Medicine Reports, 18, 4399-4409. https://doi.org/10.3892/mmr.2018.9427
MLA
Li, D., Ren, W., Jiang, Z., Zhu, L."Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury". Molecular Medicine Reports 18.5 (2018): 4399-4409.
Chicago
Li, D., Ren, W., Jiang, Z., Zhu, L."Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury". Molecular Medicine Reports 18, no. 5 (2018): 4399-4409. https://doi.org/10.3892/mmr.2018.9427
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