Open Access

SIRT1 regulates cigarette smoke extract‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway

  • Authors:
    • Fang Yang
    • Huiping Qin
    • Chaoqun Qin
    • Bing Huang
    • Feng Gao
    • Yi Liao
    • Yanping Tang
    • Yanju Mo
    • Qianjie Yang
    • Changming Wang
  • View Affiliations

  • Published online on: November 29, 2024     https://doi.org/10.3892/mmr.2024.13408
  • Article Number: 43
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

M1 macrophages activated by cigarette smoke extract (CSE) serve a pro‑inflammatory role in chronic obstructive pulmonary disease (COPD). The expression of silent information regulator 1 (SIRT1) is decreased in the alveolar macrophages of patients with COPD. However, whether SIRT1 is involved in COPD by regulating macrophage polarization remains unknown. Rat Alveolar Macrophage NR8383 cells were exposed to CSE. Cell Counting Kit‑8 assay, western blot assay and ELISA showed that with increasing concentration of CSE, the activity of NR8383 cells and expression of SIRT1 gradually decreased, while the release of inflammatory cytokines TNFα, IL‑1β and IL‑6 increased. As shown in western blot or Immunofluorescence assays, exposure to CSE also increased expression levels of the M1 markers inducible nitric oxide synthase and CD86, whereas it downregulated expression of the M2 markers arginase 1 and CD206. In addition, CSE increased expression of TNF receptor associated factor 6 (TRAF6), NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase‑1 protein in NR8383 cells. Overexpression plasmids of SIRT1 and TRAF6 significantly reversed the aforementioned changes induced by CSE. Moreover, immunoprecipitation demonstrated that TRAF6 could bind to NLRP3. The overexpression of TRAF6 notably attenuated the regulatory effects of overexpression of SIRT1 on polarization and inflammation in NR8383 cells. Conversely, overexpression of SIRT1 inhibited the TRAF6/NLRP3 signaling pathway, thereby suppressing CSE‑induced M1 polarization and release of inflammatory factors in NR8383 cells. The present study demonstrates that SIRT1 regulates CSE‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway.
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February-2025
Volume 31 Issue 2

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Spandidos Publications style
Yang F, Qin H, Qin C, Huang B, Gao F, Liao Y, Tang Y, Mo Y, Yang Q, Wang C, Wang C, et al: SIRT1 regulates cigarette smoke extract‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway. Mol Med Rep 31: 43, 2025.
APA
Yang, F., Qin, H., Qin, C., Huang, B., Gao, F., Liao, Y. ... Wang, C. (2025). SIRT1 regulates cigarette smoke extract‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway. Molecular Medicine Reports, 31, 43. https://doi.org/10.3892/mmr.2024.13408
MLA
Yang, F., Qin, H., Qin, C., Huang, B., Gao, F., Liao, Y., Tang, Y., Mo, Y., Yang, Q., Wang, C."SIRT1 regulates cigarette smoke extract‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway". Molecular Medicine Reports 31.2 (2025): 43.
Chicago
Yang, F., Qin, H., Qin, C., Huang, B., Gao, F., Liao, Y., Tang, Y., Mo, Y., Yang, Q., Wang, C."SIRT1 regulates cigarette smoke extract‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway". Molecular Medicine Reports 31, no. 2 (2025): 43. https://doi.org/10.3892/mmr.2024.13408