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TREM-1 aggravates chronic obstructive pulmonary disease development via activation NLRP3 inflammasome-mediated pyroptosis

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Abstract

Objectives

Chronic obstructive pulmonary disease (COPD) is a major cause of death globally. Inflammation plays a crucial role in COPD development. Pyroptosis, an inflammatory form of cell death, may involve in the pathogenesis of COPD. This study aims to explore the role and action mechanism of triggering receptor expressed on myeloid cells 1 (TREM-1) in COPD.

Methods

Here, cigarette smoke stimulation was used to establish COPD model in mice. Cigarette smoke extract combined with lipopolysaccharide was used to stimulate RAW264.7 cells for COPD model in vitro. QRT-PCR and Western blot were performed to detect the expression of mRNA and proteins, respectively, in the lung tissues and cells. Concentration of cytokines was measured using ELISA. H&E staining was used to analyze the pathological changes in lung tissues. The number of infiltrated macrophage was examined using immunofluorescence. LP17 was used to silence the expression of TREM-1.

Results

The results showed that TREM-1 was highly expressed in COPD. In vivo, inhibition of TREM-1 effectively improved the injury in lung tissues of COPD mouse, and reduced the infiltration of macrophages. Moreover, inhibition of TREM-1 in vivo and in vitro notably suppressed the activation of NLRP3 inflammasome and pyroptosis. Rescue experiment demonstrated that TREM-1 activated pyroptosis via regulating NLRP3 inflammasome.

Conclusion

Overall, our results proved that TREM-1 promoted the lung injury and inflammation in COPD mouse through activation of NLRP3 inflammasome-mediated pyroptosis. Our data indicated a novel mechanism of TREM-1 in COPD development, and maybe provide a novel therapeutic target for COPD treatment.

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Availability of data and materials

The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This study was supported by Hunan Provincial Natural Science Foundation of China (Grant no.2020JJ4911).

Author information

Authors and Affiliations

  1. Department of Geriatrics, Respiratory Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China

    Lijing Wang, Qiong Chen, Qiao Yu & Jian Xiao

  2. Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China

    Hongjun Zhao

Authors
  1. Lijing Wang
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  2. Qiong Chen
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  3. Qiao Yu
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  4. Jian Xiao
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  5. Hongjun Zhao
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Contributions

LW designed the study; LW, QC, QY, JX, HZ performed the study and analyzed the data; LW drafted the paper; All authors read and approved the paper.

Corresponding author

Correspondence to Hongjun Zhao.

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The authors declare no conflicts of interest.

Ethical approval

This study was approved by the Institute Research Ethics Committee of Xiangya Hospital, Central South University.

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Responsible Editor: Anatoliy Kubyshkin.

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Cite this article

Wang, L., Chen, Q., Yu, Q. et al. TREM-1 aggravates chronic obstructive pulmonary disease development via activation NLRP3 inflammasome-mediated pyroptosis. Inflamm. Res. 70, 971–980 (2021). https://doi.org/10.1007/s00011-021-01490-x

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  • DOI: https://doi.org/10.1007/s00011-021-01490-x

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