Cargando…
Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice
Ibrutinib has potential therapeutic or protective effects against viral- and bacterial-induced acute lung injury (ALI), likely by modulating the Bruton tyrosine kinase (BTK) signaling pathway. However, ibrutinib has multi-target effects. Moreover, immunity and inflammation targets in ALI treatment a...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657648/ https://www.ncbi.nlm.nih.gov/pubmed/36362264 http://dx.doi.org/10.3390/ijms232113478 |
_version_ | 1784829750082011136 |
---|---|
author | Rao, Huanan Song, Xiaominting Lei, Jieting Lu, Peng Zhao, Guiying Kang, Xin Zhang, Duanna Zhang, Tingrui Ren, Yali Peng, Cheng Li, Yuzhi Pei, Jin Cao, Zhixing |
author_facet | Rao, Huanan Song, Xiaominting Lei, Jieting Lu, Peng Zhao, Guiying Kang, Xin Zhang, Duanna Zhang, Tingrui Ren, Yali Peng, Cheng Li, Yuzhi Pei, Jin Cao, Zhixing |
author_sort | Rao, Huanan |
collection | PubMed |
description | Ibrutinib has potential therapeutic or protective effects against viral- and bacterial-induced acute lung injury (ALI), likely by modulating the Bruton tyrosine kinase (BTK) signaling pathway. However, ibrutinib has multi-target effects. Moreover, immunity and inflammation targets in ALI treatment are poorly defined. We investigated whether the BTK-, FLT3-, and EGFR-related signaling pathways mediated the protective effects of ibrutinib on ALI. The intratracheal administration of poly I:C or LPS after ibrutinib administration in mice was performed by gavage. The pathological conditions of the lungs were assessed by micro-CT and HE staining. The levels of neutrophils, lymphocytes, and related inflammatory factors in the lungs were evaluated by ELISA, flow cytometry, immunohistochemistry, and immunofluorescence. Finally, the expression of proteins associated with the BTK-, FLT3-, and EGFR-related signaling pathways were evaluated by Western blotting. Ibrutinib (10 mg/kg) protected against poly I:C-induced (5 mg/kg) and LPS-induced (5 mg/kg) lung inflammation. The wet/dry weight ratio (W/D) and total proteins in the bronchoalveolar lavage fluid (BALF) were markedly reduced after ibrutinib (10 mg/kg) treatment, relative to the poly I:C- and LPS-treated groups. The levels of ALI indicators (NFκB, IL-1β, IL-6, TNF-α, IFN-γ, neutrophils, and lymphocytes) were significantly reduced after treatment. Accordingly, ibrutinib inhibited the poly I:C- and LPS-induced BTK-, FLT3-, and EGFR-related pathway activations. Ibrutinib inhibited poly I:C- and LPS-induced acute lung injury, and this may be due to its ability to suppress the BTK-, FLT3-, and EGFR-related signaling pathways. Therefore, ibrutinib is a potential protective agent for regulating immunity and inflammation in poly I:C- and LPS-induced ALI. |
format | Online Article Text |
id | pubmed-9657648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96576482022-11-15 Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice Rao, Huanan Song, Xiaominting Lei, Jieting Lu, Peng Zhao, Guiying Kang, Xin Zhang, Duanna Zhang, Tingrui Ren, Yali Peng, Cheng Li, Yuzhi Pei, Jin Cao, Zhixing Int J Mol Sci Article Ibrutinib has potential therapeutic or protective effects against viral- and bacterial-induced acute lung injury (ALI), likely by modulating the Bruton tyrosine kinase (BTK) signaling pathway. However, ibrutinib has multi-target effects. Moreover, immunity and inflammation targets in ALI treatment are poorly defined. We investigated whether the BTK-, FLT3-, and EGFR-related signaling pathways mediated the protective effects of ibrutinib on ALI. The intratracheal administration of poly I:C or LPS after ibrutinib administration in mice was performed by gavage. The pathological conditions of the lungs were assessed by micro-CT and HE staining. The levels of neutrophils, lymphocytes, and related inflammatory factors in the lungs were evaluated by ELISA, flow cytometry, immunohistochemistry, and immunofluorescence. Finally, the expression of proteins associated with the BTK-, FLT3-, and EGFR-related signaling pathways were evaluated by Western blotting. Ibrutinib (10 mg/kg) protected against poly I:C-induced (5 mg/kg) and LPS-induced (5 mg/kg) lung inflammation. The wet/dry weight ratio (W/D) and total proteins in the bronchoalveolar lavage fluid (BALF) were markedly reduced after ibrutinib (10 mg/kg) treatment, relative to the poly I:C- and LPS-treated groups. The levels of ALI indicators (NFκB, IL-1β, IL-6, TNF-α, IFN-γ, neutrophils, and lymphocytes) were significantly reduced after treatment. Accordingly, ibrutinib inhibited the poly I:C- and LPS-induced BTK-, FLT3-, and EGFR-related pathway activations. Ibrutinib inhibited poly I:C- and LPS-induced acute lung injury, and this may be due to its ability to suppress the BTK-, FLT3-, and EGFR-related signaling pathways. Therefore, ibrutinib is a potential protective agent for regulating immunity and inflammation in poly I:C- and LPS-induced ALI. MDPI 2022-11-03 /pmc/articles/PMC9657648/ /pubmed/36362264 http://dx.doi.org/10.3390/ijms232113478 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rao, Huanan Song, Xiaominting Lei, Jieting Lu, Peng Zhao, Guiying Kang, Xin Zhang, Duanna Zhang, Tingrui Ren, Yali Peng, Cheng Li, Yuzhi Pei, Jin Cao, Zhixing Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice |
title | Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice |
title_full | Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice |
title_fullStr | Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice |
title_full_unstemmed | Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice |
title_short | Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice |
title_sort | ibrutinib prevents acute lung injury via multi-targeting btk, flt3 and egfr in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657648/ https://www.ncbi.nlm.nih.gov/pubmed/36362264 http://dx.doi.org/10.3390/ijms232113478 |
work_keys_str_mv | AT raohuanan ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT songxiaominting ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT leijieting ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT lupeng ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT zhaoguiying ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT kangxin ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT zhangduanna ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT zhangtingrui ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT renyali ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT pengcheng ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT liyuzhi ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT peijin ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice AT caozhixing ibrutinibpreventsacutelunginjuryviamultitargetingbtkflt3andegfrinmice |