Subcutaneous administration of infliximab-attenuated silica-induced lung fibrosis
Journal Title: International Journal of Occupational Medicine and Environmental Health - Year 2018, Vol 31, Issue 4
Abstract
Objectives: To investigate the influence of the anti-tumor necrosis factor-α infliximab (IFX) in the case of rats with silicosis. Material and Methods: Forty-eight Wistar rats were randomly divided into 3 groups. The study group (N = 16) – silicosis was induced by intratracheal instillation of 50 mg silica on day 1, and IFX was subcutaneously administered at a dose of 15 mg/kg of body weight from day 2 to day 6, the vehicle group (N = 16) – silica used as the study group but without IFX, the sham group (N = 16) – 1 ml of saline was intratracheal-used. Eight rats in each group were euthanized on day 7 and on day 14, respectively. Lung tissue sections were stained with hematoxylin and eosin or Masson’s trichromedye. The nuclear factor-κB p65 (NF-κB p65) positioning in the lung tissues were determined by immunohistochemical staining. Levels of tumor necrosis factor α (TNF-α) in rat serum and bronchoalveolar lavage fluid were measured with enzyme linked immunosorbent assay. The inducible nitric oxide synthase (iNOS) mRNA in the lung tissues was measured by quantitative real-time polymerase chain reaction, as well as inhibitor protein-κB (I-κB) and NF-κB p65 expression were measured quantitatively by western blotting. Results: Silica installation increased the lung tissues inflammation reaction, oxidative stress and pulmonary fibrosis. Infliximab treatment significantly improved silica-induced lung pathological changes (inflammatory cells, collagen deposition), decreased the TNF-α inhibited NF-κB signaling (I-κB, NF-κB p65) as well as oxidant status (iNOS). Conclusions: Infliximab may improve silica-induced pulmonary inflammation by decreasing the TNF-α, inhibiting NF-κB signaling (I-κB, NF-κB p65) as well as oxidant status (iNOS), which suggest that IFX has potential role in the treatment of silica-induced lung damage.
Authors and Affiliations
Hua Zhang, Jun-Na Sui, Lei Gao, Jian Guo
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