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Inhibition of gp130 alleviates LPS-induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathway

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Abstract

Background and objective

Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) is a life-threatening respiratory disease. Gp130 is a signal transduction receptor that participates in a variety of essential biological processes. The biological function of gp130 in ALI/ARDS is unclear. This study aims to investigate the roles and potential mechanisms of gp130 in lung injury induced by lipopolysaccharide (LPS).

Methods

The ALI/ARDS mouse model was established using intratracheal LPS administration. Hematoxylin and eosin staining and bronchoalveolar lavage fluid analysis were used to evaluate the degree of lung injury. Cell apoptosis was assessed by TUNEL staining, flow cytometry, and western blot. Then the expression of gp130, IL-6, IL-10, TNF-α, and the JAK1/STAT3 signaling pathway-related proteins was assessed by RT-PCR, western blot, and immunohistochemistry.

Results

The expression of gp130 increased after 24 h of LPS treatment. Inhibiting gp130 improved inflammatory infiltration and alveolar collapsed, decreased IL-6 and TNF-α levels, raised IL-10 levels, and decreased cell apoptosis in LPS-induced mice. Meanwhile, suppressing gp130 reduced the inflammatory response and cell apoptosis in LPS-induced Beas-2B cells. Furthermore, p-JAK1 and p-STAT3 expressions were elevated after LPS stimulation and decreased following gp130 inhibition, suggesting that gp130 may regulate the JAK1/STAT3 signaling pathway in LPS-induced mice and Beas-2B cells.

Conclusion

The findings suggest that gp130 regulates the inflammatory response and cell apoptosis through the JAK1/STAT3 signaling pathway, thereby mitigating LPS-induced lung injury. Gp130 may be a potential therapeutic target for ALI/ARDS.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

Abbreviations

ALI:

Acute lung injury

ARDS:

Acute respiratory distress syndrome

CNTF:

Ciliary neurotrophic factor

DMSO:

Dimethyl sulfoxide

DAPI:

4′,6-Diamidino-2-phenylindole

FBS:

Fetal bovine serum

Gp130:

Glycoprotein 130

HE:

Hematoxylin and eosin

LPS:

Lipopolysaccharide

LIF:

Leukemia inhibitory factor

PBS:

Phosphate buffer solution

PMSF:

Phenylmethyl sulfonyl fluoride

PVDF:

Polyvinylidene fluoride

RT:

Room temperature

SPF:

Specific pathogen-free

TUNEL:

TdT-mediated dUTP nick end labeling

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (grant/award number: no. 81873420, no. 82070075).

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Authors and Affiliations

  1. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, 200032, People’s Republic of China

    Fan Xu, Sijiao Wang, Yali Wang, Lijuan Hu & Lei Zhu

  2. Department of Pulmonary and Critical Care Medicine, Huadong Hospital Affiliated to Fudan University, 221 Yan An Road, Shanghai, 200040, People’s Republic of China

    Lei Zhu

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Contributions

Fan Xu: Conceptualization, Methodology, Writing–original draft, Writing–review & editing. Sijiao Wang: Conceptualization, Methodology. Lijuan Hu: Conceptualization, Visualization. Yali Wang: Methodology, Investigation. Lei Zhu: Conceptualization, Supervision, Writing – review & editing. All authors approve the final version to be submitted.

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Correspondence to Lei Zhu.

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Xu, F., Wang, S., Wang, Y. et al. Inhibition of gp130 alleviates LPS-induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathway. Inflamm. Res. 72, 493–507 (2023). https://doi.org/10.1007/s00011-022-01686-9

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