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Article

Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice

  • Authors:
    • Yanbiao Chu
    • Xiaoying Xiangli
    • Wei Xiao
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
  • Pages: 3181-3187
    |
    Published online on: December 17, 2014
       https://doi.org/10.3892/mmr.2014.3106
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Abstract

Pulmonary arterial hypertension (PAH) is a life‑threatening disease characterized by the complex proliferation of the pulmonary vascular endothelium and progressive pulmonary vascular remodeling. CD4+CD25+ regulatory T cells (Tregs) have been the focus of numerous studies into PAH. The present study aimed to investigate the role and mechanisms of Tregs in hypoxia‑induced PAH. A total of 60 male mice were divided at random into three groups: Normoxia group, hypoxia control group and Tregs group. Measurements were obtained of the right ventricle systolic pressure (RVSP) and the Fulton's index; in addition, the mRNA and protein expression of pro‑inflammatory cytokines including monocyte chemotactic protein 1 (MCP‑1), interleukin (IL)‑1β and IL‑6, as well as the anti‑inflammatory cytokine IL‑10 in the lungs were determined by reverse transcription quantitative polymerase chain reaction and western blot analysis in vivo. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic condition with or without Tregs for 48 h, and the proliferation rate and cell cycle of HPASMCs were determined. In addition, the protein levels of phosphorylated (p)‑Akt and p‑extracellular signal‑regulated kinase (ERK) were measured in HPASMCs in vitro. The results showed that Treg treatment significantly reduced the increased the hypoxia‑induced RVSP and Fulton's index, decreased pro‑inflammatory cytokine expression as well as enhanced IL‑10 levels in vivo. Furthermore, Treg treatment significantly reduced HPASMCs proliferation and the expression of cyclin D1, cyclin‑dependent kinase (CDK)4, p‑Akt and p‑ERK, as well as increased p27 expression in vitro. In conclusion, the results of the present study indicated that Tregs protected against hypoxia‑induced PAH in mice; the mechanisms of which may proceed via the suppression of the inflammatory response, as Tregs were found to enhance anti‑inflammatory cytokine levels, inhibit HPASMCs proliferation and regulate the cell cycle. These results therefore indicated that Tregs may be a potential novel target for the treatment of PAH.
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Copy and paste a formatted citation
Spandidos Publications style
Chu Y, Xiangli X and Xiao W: Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice. Mol Med Rep 11: 3181-3187, 2015.
APA
Chu, Y., Xiangli, X., & Xiao, W. (2015). Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice. Molecular Medicine Reports, 11, 3181-3187. https://doi.org/10.3892/mmr.2014.3106
MLA
Chu, Y., Xiangli, X., Xiao, W."Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice". Molecular Medicine Reports 11.4 (2015): 3181-3187.
Chicago
Chu, Y., Xiangli, X., Xiao, W."Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice". Molecular Medicine Reports 11, no. 4 (2015): 3181-3187. https://doi.org/10.3892/mmr.2014.3106
Copy and paste a formatted citation
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Spandidos Publications style
Chu Y, Xiangli X and Xiao W: Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice. Mol Med Rep 11: 3181-3187, 2015.
APA
Chu, Y., Xiangli, X., & Xiao, W. (2015). Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice. Molecular Medicine Reports, 11, 3181-3187. https://doi.org/10.3892/mmr.2014.3106
MLA
Chu, Y., Xiangli, X., Xiao, W."Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice". Molecular Medicine Reports 11.4 (2015): 3181-3187.
Chicago
Chu, Y., Xiangli, X., Xiao, W."Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice". Molecular Medicine Reports 11, no. 4 (2015): 3181-3187. https://doi.org/10.3892/mmr.2014.3106
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