Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery

In Kyoung Kim; Chin Kook Rhee; Chang Dong Yeo; Hyeon Hui Kang; Dong Gun Lee; Sang Haak Lee; Jin Woo Kim

doi:10.1186/cc12786

Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery

In Kyoung Kim, Chin Kook Rhee, Chang Dong Yeo, Hyeon Hui Kang, Dong Gun Lee, Sang Haak Lee, Jin Woo Kim

Department of Internal Medicine

The Catholic University of Korea

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

Introduction: Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice.Methods: Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined.Results: Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-β and c-KIT in imatinib or nilotinib group were significantly lower than LPS group.Conclusions: Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.

Original language	English
Article number	R114
Journal	Critical Care
Volume	17
Issue number	3
DOIs	https://doi.org/10.1186/cc12786
State	Published - 20 Jun 2013

Bibliographical note

Funding Information:
The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2012. We thank Novartis Pharmaceuticals (Basel, Switzerland) for donating the raw drug material for the present study. Novartis Pharmaceuticals played no role in the study design, or the collection, analysis, or interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication.

Keywords

Acute lung injury
imatinib
neutropenia recovery
nilotinib
platelet-derived growth factor receptor (PDGFR)

Access to Document

10.1186/cc12786

Cite this

@article{7d673db21508447cb74530a6d55b12f1,

title = "Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery",

abstract = "Introduction: Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice.Methods: Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined.Results: Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-β and c-KIT in imatinib or nilotinib group were significantly lower than LPS group.Conclusions: Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.",

keywords = "Acute lung injury, imatinib, neutropenia recovery, nilotinib, platelet-derived growth factor receptor (PDGFR)",

author = "Kim, {In Kyoung} and Rhee, {Chin Kook} and Yeo, {Chang Dong} and Kang, {Hyeon Hui} and Lee, {Dong Gun} and Lee, {Sang Haak} and Kim, {Jin Woo}",

note = "Funding Information: The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2012. We thank Novartis Pharmaceuticals (Basel, Switzerland) for donating the raw drug material for the present study. Novartis Pharmaceuticals played no role in the study design, or the collection, analysis, or interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication.",

year = "2013",

month = jun,

day = "20",

doi = "10.1186/cc12786",

language = "English",

volume = "17",

journal = "Critical Care",

issn = "1364-8535",

publisher = "BioMed Central Ltd.",

number = "3",

}

TY - JOUR

T1 - Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery

AU - Kim, In Kyoung

AU - Rhee, Chin Kook

AU - Yeo, Chang Dong

AU - Kang, Hyeon Hui

AU - Lee, Dong Gun

AU - Lee, Sang Haak

AU - Kim, Jin Woo

N1 - Funding Information: The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2012. We thank Novartis Pharmaceuticals (Basel, Switzerland) for donating the raw drug material for the present study. Novartis Pharmaceuticals played no role in the study design, or the collection, analysis, or interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication.

PY - 2013/6/20

Y1 - 2013/6/20

N2 - Introduction: Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice.Methods: Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined.Results: Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-β and c-KIT in imatinib or nilotinib group were significantly lower than LPS group.Conclusions: Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.

AB - Introduction: Neutrophil recovery has been implicated in deterioration of oxygenation and exacerbation of preexisting acute lung injury (ALI). The aim of this study was to investigate whether imatinib or nilotinib was effective on lipopolysaccharide (LPS)-induced ALI during neutropenia recovery in mice.Methods: Mice were rendered neutropenic with cyclophosphamide prior to the intratracheal instillation of LPS. Imatinib or nilotinib was administrated by oral gavage during neutropenia recovery. In order to study the effects of drugs, mice were killed on day 5 and blood, bronchoalveolar lavage (BAL) fluid and lung tissue samples were obtained. The lung wet/dry weight ratio and protein levels in the BAL fluid or lung tissue were determined.Results: Treatment with imatinib or nilotinib significantly attenuated the LPS-induced pulmonary edema, and this result was supported by the histopathological examination. The concentrations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and myeloperoxidase in BAL fluid were significantly inhibited by imatinib or nilotinib in mice of ALI during neutropenia recovery. The mRNA expressions of platelet-derived growth factor receptor-β and c-KIT in imatinib or nilotinib group were significantly lower than LPS group.Conclusions: Our data indicated that imatinib or nilotinib effectively attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the therapeutic potential of imatinib and nilotinib in ALI during neutropenia recovery.

KW - Acute lung injury

KW - imatinib

KW - neutropenia recovery

KW - nilotinib

KW - platelet-derived growth factor receptor (PDGFR)

UR - http://www.scopus.com/inward/record.url?scp=84879086917&partnerID=8YFLogxK

U2 - 10.1186/cc12786

DO - 10.1186/cc12786

M3 - Article

C2 - 23787115

AN - SCOPUS:84879086917

SN - 1364-8535

VL - 17

JO - Critical Care

JF - Critical Care

IS - 3

M1 - R114

ER -

Effect of tyrosine kinase inhibitors, imatinib and nilotinib, in murine lipopolysaccharide-induced acute lung injury during neutropenia recovery

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this