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Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice
INTRODUCTION: Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury (ALI). CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. The purpose of this study was to inv...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Termedia Publishing House
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949915/ https://www.ncbi.nlm.nih.gov/pubmed/29765453 http://dx.doi.org/10.5114/aoms.2017.64980 |
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author | Cao, Qing Li, Biru Wang, Xike Sun, Kun Guo, Ying |
author_facet | Cao, Qing Li, Biru Wang, Xike Sun, Kun Guo, Ying |
author_sort | Cao, Qing |
collection | PubMed |
description | INTRODUCTION: Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury (ALI). CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. The purpose of this study was to investigate the functional relevance of the CXCR2 inhibitor SB225002 in LPS-induced acute lung injury. MATERIAL AND METHODS: Male C57BL/6 mice were randomly divided into the following four experimental groups (n = 10 per group): untreated group (control group, Ctr); LPS-treated ALI group (LPS group, LPS); LPS + PBS-treated group (LPS + PBS); and SB225002-treated ALI group (LPS + SB225002). Twenty-four hours after treatment, the blood, bronchoalveolar lavage fluid (BALF), and lung tissue were collected and wet/dry ratio, protein concentration, myeloperoxidase (MPO) activity, neutrophil infiltration, and inflammatory cytokine secretion in lung tissue were measured. The pathologic changes in the lungs were examined using optical microscopy. Survival rates were recorded at 120 h in all four groups, in other experiments. RESULTS: Histology findings revealed that the SB225002-treated group had significantly milder lung injury compared to the LPS-induced ALI and the PBS-treated control groups. Treatment with SB225002 significantly attenuated LPS-induced lung injury and suppressed the inflammatory responses in damaged lung tissue. Compared to the PBS-treated control group, treatment with SB225002 dramatically decreased the lung wet/dry ratio, protein concentration, and infiltration of neutrophils in lung tissue. Therefore, SB225002 treatment appeared to inhibit the production of inflammatory cytokines and increase survival time compared to the PBS-treated control group. CONCLUSIONS: Together, these data demonstrated that inhibition of CXCR2 signaling by SB225002 could ameliorate LPS-induced acute lung injury, by reducing neutrophil recruitment and vascular permeability. SB225002 may be further developed as a potential novel treatment for LPS-induced ALI. |
format | Online Article Text |
id | pubmed-5949915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Termedia Publishing House |
record_format | MEDLINE/PubMed |
spelling | pubmed-59499152018-05-14 Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice Cao, Qing Li, Biru Wang, Xike Sun, Kun Guo, Ying Arch Med Sci Experimental Research INTRODUCTION: Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury (ALI). CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. The purpose of this study was to investigate the functional relevance of the CXCR2 inhibitor SB225002 in LPS-induced acute lung injury. MATERIAL AND METHODS: Male C57BL/6 mice were randomly divided into the following four experimental groups (n = 10 per group): untreated group (control group, Ctr); LPS-treated ALI group (LPS group, LPS); LPS + PBS-treated group (LPS + PBS); and SB225002-treated ALI group (LPS + SB225002). Twenty-four hours after treatment, the blood, bronchoalveolar lavage fluid (BALF), and lung tissue were collected and wet/dry ratio, protein concentration, myeloperoxidase (MPO) activity, neutrophil infiltration, and inflammatory cytokine secretion in lung tissue were measured. The pathologic changes in the lungs were examined using optical microscopy. Survival rates were recorded at 120 h in all four groups, in other experiments. RESULTS: Histology findings revealed that the SB225002-treated group had significantly milder lung injury compared to the LPS-induced ALI and the PBS-treated control groups. Treatment with SB225002 significantly attenuated LPS-induced lung injury and suppressed the inflammatory responses in damaged lung tissue. Compared to the PBS-treated control group, treatment with SB225002 dramatically decreased the lung wet/dry ratio, protein concentration, and infiltration of neutrophils in lung tissue. Therefore, SB225002 treatment appeared to inhibit the production of inflammatory cytokines and increase survival time compared to the PBS-treated control group. CONCLUSIONS: Together, these data demonstrated that inhibition of CXCR2 signaling by SB225002 could ameliorate LPS-induced acute lung injury, by reducing neutrophil recruitment and vascular permeability. SB225002 may be further developed as a potential novel treatment for LPS-induced ALI. Termedia Publishing House 2017-01-06 2018-04 /pmc/articles/PMC5949915/ /pubmed/29765453 http://dx.doi.org/10.5114/aoms.2017.64980 Text en Copyright: © 2017 Termedia & Banach http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license. |
spellingShingle | Experimental Research Cao, Qing Li, Biru Wang, Xike Sun, Kun Guo, Ying Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice |
title | Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice |
title_full | Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice |
title_fullStr | Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice |
title_full_unstemmed | Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice |
title_short | Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice |
title_sort | therapeutic inhibition of cxc chemokine receptor 2 by sb225002 attenuates lps-induced acute lung injury in mice |
topic | Experimental Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949915/ https://www.ncbi.nlm.nih.gov/pubmed/29765453 http://dx.doi.org/10.5114/aoms.2017.64980 |
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