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Effects of Tec Tyrosine Kinase Inhibition on the Inflammatory Response of Severe Acute Pancreatitis-Associated Acute Lung Injury in Mice

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Abstract

Background

The Tec kinase family is involved in acute and chronic inflammatory diseases, but its relationship with severe acute pancreatitis (SAP) remains unclear.

Aims

To investigate whether Tec tyrosine kinase can be used as a target for severe acute pancreatitis-associated acute lung injury (PALI).

Methods

A total of 90 mice were randomly assigned into four groups: SAP (n = 15), control (n = 15), SAP + α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13) (pretreated with Tec kinase inhibitor LFM-A13, n = 15), and SAP + Tec siRNA (pretreated with PBS/negative control siRNA/Tec siRNA, n = 45). SAP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 0, 3, 24, 48, and 72 h, respectively. Pathological changes and scores of the lung and pancreas were determined using hematoxylin–eosin staining. Expression of Tec and phosphorylated Tec (p-Tec) were examined by real-time polymerase chain reaction, Western blot, and immunoprecipitation. Serum levels of amylase, myeloperoxidase, and pro-inflammatory cytokines were measured by ELISA.

Results

The expression of Tec in lung tissue was significantly higher in the SAP group than in the control group (p < 0.05), and p-Tec expression gradually increased with time. Furthermore, p-Tec expression was significantly lower in the SAP + LFM-A13 group than in the SAP group (p < 0.05); however, Tec expression did not vary. Tec inhibitors, LFM-A13 and Tec siRNA, alleviated pathological damage and release of inflammatory cytokines (p < 0.05).

Conclusions

Tec tyrosine kinase plays a key role in PALI, and is therefore a potential target for clinical treatment.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81470882). I would like to express many thanks to my classmate Shuo Sha and she contributed equally to this work. At the same time, Prof. Yan Zhang in Changhai Hospital of the Second Military Medical University and Peiyu Han in Jiang Nan University also help me a lot during the experiment.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81470882).

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Authors and Affiliations

  1. Department of Gastroenterology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong Province, China

    Yiteng Meng, Shuo Sha, Jing Yang & Hongbo Ren

Authors
  1. Yiteng Meng
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  2. Shuo Sha
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  3. Jing Yang
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  4. Hongbo Ren
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Contributions

Hongbo Ren designed the research. Yiteng Meng participated in animal experiments and wrote the paper. Shuo Sha and Jing Yang performed research and analyzed data.

Corresponding author

Correspondence to Hongbo Ren.

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The authors declare that they have no conflict of interest.

Ethical statement

The present study was approved by the Research Ethics Committee of Qilu Hospital of Shandong University (KYLL-2014(KS)-050).

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Meng, Y., Sha, S., Yang, J. et al. Effects of Tec Tyrosine Kinase Inhibition on the Inflammatory Response of Severe Acute Pancreatitis-Associated Acute Lung Injury in Mice. Dig Dis Sci 64, 2167–2176 (2019). https://doi.org/10.1007/s10620-019-05524-7

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  • DOI: https://doi.org/10.1007/s10620-019-05524-7

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