Macrophage migration inhibitory factor (MIF) inhibition can attenuates pulmonary fibrosis, but the antifibrotic mechanism is unclear. Here we investigated antifibrotic effect of MIF knockdown in Bleomycin (BLM)-induced pulmonary fibrosis rats. The result showed that MIF inhibition attenuated lung injury and extracellular matrix deposition, significantly reduced the levels of cytokines including Transforming growth factor-β1(TGF-β1), TNF-α, IL-17, hydroxyproline (hyp), fibroblast growth factor 23 (FGF23) and secreted phosphoprotein 1 (Spp1), and inhibited the expression of CD68, F4/80 and α-smooth muscle actin(α-SMA) protein. MIF inhibition is associated with reduction of pro-inflammatory mediators and macrophage infiltration in lungs. In addition, MIF knockdown in the Day14 group was significantly better than MIF knockdown in Day1 group in terms of the above cytokines. MIF knockdown in Day14 group showed a better trend than MIF knockdown in Day1 group in inhibition of hyp and α-SMA formation. Furthermore, MIF inhibition induced down-regulated the FGF23, Spp1, Itga10, Lama1, Thbs2, Serpinb5 mRNA level and p-Smad2/3 protein level. MIF knockdown may inhibit fibrosis through the TGF-β1/Smads signaling pathway. What' more, MIF inhibition protects also against vascular remodeling via Thbs2 and Serpinb5 signaling. In summary, our study showed that knockdown of MIF can significantly inhibit lung inflammation and fibrosis in BLM-induced pulmonary fibrosis rats. The future development of inhibitors targeting MIF may contribute to the treatment of pulmonary fibrosis.
Blood Mononuclear Cell Nitric Oxide Production and Plasma Cytokine Levels in Healthy Gabonese Children with Prior Mild or Severe Malaria