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Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice.
Arch Med Sci. 2018 Apr; 14(3):635-644.AM

Abstract

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.

Authors+Show Affiliations

Department of Pediatrics, Shanghai Jiao Tong University Affiliated Shanghai Children's Medical Center, Shanghai, China.Department of Pediatrics, Shanghai Jiao Tong University Affiliated Shanghai Children's Medical Center, Shanghai, China.Department of Pediatric Cardiology, Shanghai Jiao Tong University Affiliated Shanghai Children's Medical Center, Shanghai, China.Department of Pediatric Cardiology, Shanghai Jiao Tong University Affiliated Xinhua Hospital, Shanghai, China.Department of Pediatric Cardiology, Shanghai Jiao Tong University Affiliated Shanghai Children's Medical Center, Shanghai, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29765453

Citation

Cao, Qing, et al. "Therapeutic Inhibition of CXC Chemokine Receptor 2 By SB225002 Attenuates LPS-induced Acute Lung Injury in Mice." Archives of Medical Science : AMS, vol. 14, no. 3, 2018, pp. 635-644.
Cao Q, Li B, Wang X, et al. Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice. Archives of medical science : AMS. 2018;14(3):635-644.
Cao, Q., Li, B., Wang, X., Sun, K., & Guo, Y. (2018). Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice. Archives of Medical Science : AMS, 14(3), 635-644. https://doi.org/10.5114/aoms.2017.64980
Cao Q, et al. Therapeutic Inhibition of CXC Chemokine Receptor 2 By SB225002 Attenuates LPS-induced Acute Lung Injury in Mice. Archives of medical science : AMS. 2018;14(3):635-644. PubMed PMID: 29765453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic inhibition of CXC chemokine receptor 2 by SB225002 attenuates LPS-induced acute lung injury in mice. AU - Cao,Qing, AU - Li,Biru, AU - Wang,Xike, AU - Sun,Kun, AU - Guo,Ying, Y1 - 2017/01/06/ PY - 2014/07/07/received PY - 2014/12/15/accepted PY - 2018/5/17/entrez PY - 2018/5/17/pubmed PY - 2018/5/17/medline KW - CXCR2 KW - LPS-induced ALI KW - SB225002 KW - neutrophil migration SP - 635 EP - 644 JF - Archives of medical science : AMS VL - 14 IS - 3 N2 - 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. SN - 1734-1922 UR - https://www.unboundmedicine.com/medline/citation/29765453/Therapeutic_inhibition_of_CXC_chemokine_receptor_2_by_SB225002_attenuates_LPS_induced_acute_lung_injury_in_mice_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29765453/ DB - PRIME DP - Unbound Medicine ER -
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