Bone marrow mesenchymal stem cells inhibited bleomycin-induced lung fibrosis

Abstract

The present study was performed to evaluate the protective effect of bone marrow mesenchymal stem cells (BMSCs), TLR2-silencing BMSCs (BMSC^TLR2−/−), on bleomycin (BLM)-induced lung fibrosis and elucidate the critical role of TLR2 during the process. The BMSCs were isolated from adult male SD rats, and BMSC^TLR2−/− was constructed. Rats were intratracheally instilled with BLM. Then, 5 × 10⁶ BMSCs and 5 × 10⁶ BMSC^TLR2−/− were injected into the tail vein 12 hours after the BLM challenge. All mice were sacrificed 21 days post BLM stimulation. As a result, treatment with BMSCs, but not with BMSC^TLR2−/−, markedly ameliorated lung myeloperoxidase (MPO) activity, the wet-to-dry weight (W/D) ratio, and pulmonary histopathological alterations. Additionally, the protective effect of BMSCs might be attributed to the down-regulations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), reactive oxygen species (ROS), and malondialdehyde (MDA) and the up-regulation of super-oxide dismutase (SOD). Furthermore, the administration of BMSC remarkably decreased the protein levels of MMP-3, MMP-9, TGF-β, p-smad3, p-IκB, and p-NF-κB, whereas the administration of BMSC^TLR2−/− exhibited no significant effect on the expressions of the abovementioned proteins. In conclusion, our results suggested that BMSCs exhibited a protective effect on BLM-induced pulmonary fibrosis, and TLR2 signaling might play an important role during this etiology.