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. 2016:2016:5302069.
doi: 10.1155/2016/5302069. Epub 2016 Jul 31.

Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

Fu-Chao Liu  1 , Chih-Wen Zheng  1 , Huang-Ping Yu  1
Affiliations

Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

Fu-Chao Liu et al. Biomed Res Int. 2016.

Abstract

Objectives. The peroxisome proliferator-activated receptor gamma (PPARγ) pathway exerts anti-inflammatory effects in response to injury. Maraviroc has been shown to have potent anti-inflammatory effects. The aim of this study was to investigate whether PPARγ plays an important role in maraviroc-mediated lung protection following trauma-hemorrhage. Methods. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARγ inhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered. Lung water content, tissue histology, and other various parameters were measured (n = 8 rats/group) 24 hours after resuscitation. One-way ANOVA and Tukey's testing were used for statistical analysis. Results. Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1β levels. These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats. Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury. Conclusion. These results suggest that PPARγ might play a key role in maraviroc-mediated lung protection following trauma-hemorrhage.

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Figures

Figure 1
Figure 1
Lung water content (wet to dry) in rats at 24 hours after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H). Animals were treated with either vehicle (Veh), maraviroc (Ma), maraviroc in combination with GW9662 (Ma + G), or GW9662 (G). Data are shown as mean ± SEM of 8 rats in each group. ∗ p < 0.05 compared to Sham; # p < 0.05 compared to T-H + Veh, T-H + Ma + G, and T-H + G.
Figure 2
Figure 2
Effect of maraviroc treatment on lung MPO activity in rats at 24 hours after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H). Animals were treated with either vehicle (Veh), maraviroc (Ma), maraviroc in combination with GW9662 (Ma + G), or GW9662 (G). Data are shown as mean ± SEM of 8 rats in each group. ∗ p < 0.05 compared to Sham; # p < 0.05 compared to T-H + Veh, T-H + Ma + G, and T-H + G.
Figure 3
Figure 3
ICAM-1 activities in the lungs of rats after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H). Animals were treated with either vehicle (Veh), maraviroc (Ma), maraviroc in combination with GW9662 (Ma + G), or GW9662 (G). Data are shown as mean ± SEM of 8 rats in each group. ∗ p < 0.05 compared to Sham; # p < 0.05 compared to T-H + Veh, T-H + Ma + G, and T-H + G.
Figure 4
Figure 4
IL-6 levels in the lungs of rats after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H). Animals were treated with either vehicle (Veh), maraviroc (Ma), maraviroc in combination with GW9662 (Ma + G), or GW9662 (G). Data are shown as mean ± SEM of 8 rats in each group. ∗ p < 0.05 compared to Sham; # p < 0.05 compared to T-H + Veh, T-H + Ma + G, and T-H + G.
Figure 5
Figure 5
IL-1β expression in the lungs of rats after sham operation (Sham) or trauma-hemorrhage and resuscitation (T-H). Animals were treated with either vehicle (Veh), maraviroc (Ma), maraviroc in combination with GW9662 (Ma + G), or GW9662 (G). Data are shown as mean ± SEM of 8 rats in each group. ∗ p < 0.05 compared to Sham; # p < 0.05 compared to T-H + Veh.
Figure 6
Figure 6
Representative photomicrographs of lungs of sham animals receiving vehicle (a), sham animals receiving maraviroc (b), trauma-hemorrhage animals receiving vehicle (c), trauma-hemorrhage animals receiving maraviroc (d), trauma-hemorrhage animals receiving maraviroc and GW9662 (e), and trauma-hemorrhage animals receiving GW9662 (f). Animals were sacrificed 24 hours after sham operation or trauma-hemorrhage with resuscitation. Lungs were removed and processed as described in Section 2. Lung sections were stained with hematoxylin-eosin, examined at an original magnification of ×200, and photographed.
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References

    1. Johnson R. F., Jr., Gustin J. Acute lung injury and acute respiratory distress syndrome requiring tracheal intubation and mechanical ventilation in the intensive care unit: impact on managing uncertainty for patient-centered communication. American Journal of Hospice and Palliative Medicine. 2013;30(6):569–575. doi: 10.1177/1049909112460566. - DOI - PubMed
    1. Hukkanen R. R., Liggitt H. D., Murnane R. D., Frevert C. W. Systemic inflammatory response syndrome in nonhuman primates culminating in multiple organ failure, acute lung injury, and disseminated intravascular coagulation. Toxicologic Pathology. 2009;37(6):799–804. doi: 10.1177/0192623309343778. - DOI - PMC - PubMed
    1. Barlos D., Deitch E. A., Watkins A. C., et al. Trauma-hemorrhagic shock-induced pulmonary epithelial and endothelial cell injury utilizes different programmed cell death signaling pathways. American Journal of Physiology—Lung Cellular and Molecular Physiology. 2009;296(3):L404–L417. doi: 10.1152/ajplung.00491.2007. - DOI - PMC - PubMed
    1. Reino D. C., Pisarenko V., Palange D., et al. Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice. PLoS ONE. 2011;6(8) doi: 10.1371/journal.pone.0014829.e14829 - DOI - PMC - PubMed
    1. Schröder C., Pierson R. N., III, Nguyen B.-N. H., et al. CCR5 blockade modulates inflammation and alloimmunity in primates. Journal of Immunology. 2007;179(4):2289–2299. doi: 10.4049/jimmunol.179.4.2289. - DOI - PubMed

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