Effects Of IFN-γ On TNF-α And Expression Of TGF-β₁ In Experimental Silicosis Mice

Objective:According to silicosis model of mice reproduced by tratracheal injection method, our experiment studied antagonistic mechanism ofγ-Interferon (IFN-γ) against Tumor necrosis factor-α(TNF-α) and Transforming growth factor-β₁ (TGF-β₁) and the prophylactic therapeutic effect of,γ-interferon on experimental silicosis of mice, to prove up a new approach of treating lung fibrosis.Methods:1. Female mice all came from animal experimental ministry of Jilin University. Mice exposed to lower dose of quartz by intra tracheal injection were divided into three groups randomly. They were saline normal control group, quartz exposed group,γ-Interferon prophylactic treating group. After the mice model of silicosis was established by intratracheal infusion of silica dust suspension, six mices from each group were sacrificed at 7d,14d,21d and 28 d.2. After treating with IFN-γfor 7d, 14d, 21d and 28d. we killed 6 pcs mice in each group. We removed the eyes and collected serum of these mice in the narcosis, and then make the BLAF. Applying the ELISA and SABC to measure the model of silicosis, the level of the TNF-αin the the BLAF and the albumen of the TGF-β₁ in the lung.3. Statistical analysis methods we utilized were analysis of variance using SPSS10. software and then significant difference was examined by Q test. Differences were considered to be significant at P <0.05.Results:1. Pathology inspect for lung :the fibrosis degree of silicosis is lower than the group with quartz after inbreatheing silicon dioxide powder for7, 14, 21, 28days .2. The measurements of TNF-αin BLAF: Comparing with the inbreatheing SiO₂ group and the IFN-γtreatment group, the content of TNF-αin BLAF or in the saline, the changes is distinct. Rush hour is the 7th. During the treatment withγ-IFN, the leavel of TNF-αis lower than the inbreatheing SiO₂ group, but higher than the other groups.3. The leavel of the TNF-αand TGF-β₁ in the lung: Quantity image analysis showed that from7, 14, to 21, 28 days, integrated OD positive cell of the inbreatheing SiO₂ group and the IFN-γtreatment group is increased than the comparison group (P<0.05orP<0.01). TGF-β₁ integrated OD positive cell in the lung treated with IFN-γis lower than the quartz group (P<0.05orP<0.01), but it'higher than the comparison group.Pathology inspect for lung: the fibrosis degree of silicosis is lower than the group with quartz after inbreatheing silicon dioxide powder for 7, 14, 21, 28days.DiscussionIn the past several years, there were important improvements in the researches of mechanism of lung fibrosis. Especially many kinds of cells and cytokines in the lung played an important role in this complex process,thereby the conceptions of I type and II type cytokines were put forward.IFN-γwas prototypic type I cytokine,secreted by lymphocytes and nature killing cells, and had strong inununoregulatory effect, considered as potential anti-fibrotic effect. Its possible mechanism included: (1)anti-fibrogenic activity of type II cytokines; (2)anti-collegenous effect of TGF-β₁; (3) inhibit collegenation of fibroblasts. Type II cytokines and TGF-β₁ play a critical role in the pathogenesis of lung fibrosis through stimulation of collagen and fibronectin production in fibroblasts .Our experiments observed the prophylactic therapeutic effect of IFN-γon silicotic lung of mice for 7d, 14d, 21d and 28d. The results showed that the hydroxypro-line content in IFN-γtreating groups were significantly lower than that of quartz exposed groups at 7d, 14d, 21d and 28d after instillation. Pathologic sectionsrevealed that the fibrotic degree in IFN-γtreating group was obviously lighter than that of quartz group. We might conclude that IFN-γcould reduce thehydroxyproline content in silicotic lung,and it might have some antagonistic effect on fibrosis model. In the immunochemical results,it was also showed that at these four time points,the integrated OD totals of TGF-β₁ posifive cell in IFN-γtreating groups were lower than those of quartz groups, and the differences were of significance. Therefore, IFN-γmight inhibit the improvement of lung fibrosis by means of preventing the expressions of TNF-αand TGF-β₁ in lung of silicotic mice.Conclusion1.γ-Interferon may restrain the process of lung fibrosis.2.γ-Interferon may inhibit the improvement of lung fibrosis by means of preventing the expression of TNF-αand TGF-β₁ in mice of silicotic fibrosis.