Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis
Shin-Hwa Lee, An-Soo Jang, Young-Eun Kim, Ji-Yeon Cha, Tae-Hoon Kim, Seok Jung, Seong-Kyu Park, You-Kyoung Lee, Jong-Ho Won, Yong-Hoon Kim, Choon-Sik Park, Shin-Hwa Lee, An-Soo Jang, Young-Eun Kim, Ji-Yeon Cha, Tae-Hoon Kim, Seok Jung, Seong-Kyu Park, You-Kyoung Lee, Jong-Ho Won, Yong-Hoon Kim, Choon-Sik Park
Abstract
Background: No effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production.
Methods: BMDMSCs were transferred 4 days after BLM inhalation. Wet/dry ratio, bronchoalveolar lavage cell profiles, histologic changes and deposition of collagen were analyzed.
Results: Nitrite, nitrate and cytokines were measured weekly through day 28. At day 7, the wet/dry ratio, neutrophilic inflammation, and amount of collagen were elevated in BLM-treated rats compared to sham rats (p = 0.05-0.002). Levels nitrite, nitrate, IL-1beta, IL-6, TNF-alpha, TGF-beta and VEGF were also higher at day 7 (p < 0.05). Degree of lymphocyte and macrophage infiltration increased steadily over time. BMDMSC transfer significantly reduced the BLM-induced increase in wet/dry ratio, degree of neutrophilic infiltration, collagen deposition, and levels of the cytokines, nitrite, and nitrate to those in sham-treated rats (p < 0.05). Fluorescence in situ hybridization localized the engrafted cells to areas of lung injury.
Conclusion: Systemic transfer of BMDMSCs effectively reduced the BLM-induced lung injury and fibrosis through the down-regulation of nitric oxide metabolites, and proinflammatory and angiogenic cytokines.
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References
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