Rat bone mesenchymal stem cells exert antiproliferative effects on nicotine‑exposed T cells via iNOS production

  • Authors:
    • Xiaoyan Li
    • Jianying Xu
    • Pingping Li
  • View Affiliations

  • Published online on: March 13, 2020     https://doi.org/10.3892/mmr.2020.11027
  • Pages: 2267-2275
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Abstract

Adoptive transfer of bone marrow‑derived mesenchymal stem cells (BMSCs) significantly alleviates smoking‑induced chronic obstructive pulmonary disease (COPD) in rats. Considering the critical roles of T cells during COPD development, the present study aimed to further identify the molecular mechanisms underlying the antiproliferative effect of BMSCs on splenic T cells isolated from rats following chronic exposure to nicotine. Splenic T cells were co‑cultured with rat BMSCs at various ratios and subsequently, T‑cell proliferation was measured using the Cell Counting Kit‑8 assay. The effects of the inducible nitric oxide synthase (iNOS) inhibitor N‑nitro‑L‑arginine methylester (L‑NAME) and short hairpin (sh)RNA‑lentivirus‑mediated knockdown of iNOS in BMSCs on T‑cell proliferation were evaluated. The expression levels of iNOS and STAT5 phosphorylation in BMSCs and T cells, respectively, were assessed by reverse transcription‑quantitative PCR and western blotting. A higher ratio of BMSCs to T cells resulted in increased inhibition of T‑cell proliferation; therefore, the ratio of 1:20 was selected for further in vitro experiments. At a dose of 5 µM, L‑NAME displayed the strongest ability to reverse the antiproliferative effects of BMSCs in the co‑culture system. Both L‑NAME treatment and shRNA‑mediated knockdown of iNOS expression significantly decreased the suppressive effects of BMSCs, downregulated iNOS expression at the mRNA and protein levels in BMSCs, and enhanced STAT5 phosphorylation in T cells. BMSCs inhibited the proliferation of nicotine‑exposed T cells, which was associated with iNOS expression in BMSCs and decreased STAT5 phosphorylation in T cells. The present study indicated the potential mechanisms underlying the beneficial effects of BMSC infusion in patients with chronic smoking‑induced COPD and emphysema.

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May 2020
Volume 21 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Li, X., Xu, J., & Li, P. (2020). Rat bone mesenchymal stem cells exert antiproliferative effects on nicotine‑exposed T cells via iNOS production. Molecular Medicine Reports, 21, 2267-2275. https://doi.org/10.3892/mmr.2020.11027
MLA
Li, X., Xu, J., Li, P."Rat bone mesenchymal stem cells exert antiproliferative effects on nicotine‑exposed T cells via iNOS production". Molecular Medicine Reports 21.5 (2020): 2267-2275.
Chicago
Li, X., Xu, J., Li, P."Rat bone mesenchymal stem cells exert antiproliferative effects on nicotine‑exposed T cells via iNOS production". Molecular Medicine Reports 21, no. 5 (2020): 2267-2275. https://doi.org/10.3892/mmr.2020.11027