Interleukin-12 is not essential for silicosis in mice.
Interleukin-12 is not essential for silicosis in mice.
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白介素12对于小鼠中的硅氧化症不是必不可少的。
DOI：
10.1186/1743-8977-3-2
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发表时间：
2006-01-05
影响因子：
10
通讯作者：
Rincon, Mercedes
中科院分区：
文献类型：
--
作者：
Davis, Gerald S;Pfeiffer, Linda M;Hemenway, David R;Rincon, Mercedes
矽肺的特点是炎症灶，巨噬细胞和淋巴细胞先于和伴随成纤维细胞增殖，肺泡上皮细胞增生，结缔组织基质物质沉积增多。在吸入二氧化硅后的小鼠中，自然杀伤细胞、B-细胞、CD4+和CD8+细胞聚集到肺泡腔，支气管相关淋巴组织(BALT)增大，淋巴细胞聚集在小气道和血管周围。招募的肺淋巴细胞中有相当一部分会产生干扰素-γ(干扰素-γ)，并且干扰素-γ基因缺失的小鼠患矽肺的几率比野生型小鼠要少。白介素12(IL-12)是推动获得性免疫反应向TH1样表型转化的重要途径。我们推测，IL-12可能刺激淋巴细胞活化和干扰素-γ的上调，从而成为矽肺的重要介质。将C57BL/6野生型(WT)和IL-12缺陷型(IL-12 KO)小鼠吸入假空气或微晶硅(61 mg/m~3)，连续染毒12天，每天5小时，然后于染毒后1~112天进行研究。暴露在假空气中的小鼠在所有时间点的肺组织学都是正常的。WT小鼠暴露于二氧化钛(72 mg/m~3)后，肺巨噬细胞聚集，但肺胶原蛋白未见增加。暴露于二氧化硅的WT和IL-12KO小鼠均表现出相似的进行性肺病理改变，肺湿重增加，肺总胶原(羟脯氨酸)增加。接触二氧化硅后，两个品系的IL-12p35mRNA均未见增加；二氧化硅暴露后，WT小鼠IL-12p40mRNA表达上调，而IL-12KO小鼠则呈结构性缺失。染矽尘后IL-18mRNA表达无明显变化。IL-15(天然免疫、自然杀伤细胞激活和干扰素-γ产生的重要驱动力)在暴露于空气的小鼠中大量表达，在矽肺小鼠的肺中略有增加。IL-12驱动干扰素-γ产生的轴对于暴露在晶体硅气溶胶中的小鼠矽肺的全部表现并不是必不可少的。
Silicosis features foci of inflammation where macrophages and lymphocytes precede and accompany fibroblast proliferation, alveolar epithelial hyperplasia, and increased deposition of connective tissue matrix material. In the mouse following silica inhalation there is recruitment of natural killer-, B-, and CD4+ and CD8+ lymphocytes to the alveolar spaces, enlargement of bronchial-associated lymphoid tissues (BALT), and aggregation of lymphocytes surrounding small airways and blood vessels. A substantial fraction of the recruited lung lymphocytes produce interferon-γ (IFN-γ), and IFN-γ gene-deleted mice develop less silicosis than wild-type mice. Interleukin-12 (IL-12) is an important pathway for driving the adaptive immune response towards a TH1-like phenotype. We hypothesized that IL-12 might stimulate lymphocyte activation and the up-regulation of IFN-γ, and consequently be an essential mediator for silicosis. C57Bl/6 wild-type (WT) and IL-12 deficient (IL-12 KO) mice were exposed to sham-air or crystobalite silica (61 mg/m3) by inhalation for 5 hours/day for 12 days and then studied from 1 to 112 days after exposure. Mice exposed to sham-air had normal lung histology at all time points. WT mice exposed to titanium dioxide (72 mg/m3) showed pulmonary macrophage recruitment but no increase in lung collagen. Both WT and IL-12 KO mice exposed to silica showed similar progressive lung pathology, increased wet lung weight and increased total lung collagen (hydroxyproline). IL-12 p35 mRNA was not increased in either strain after silica exposure; IL-12 p40 mRNA was up-regulated after silica in WT mice and constitutively absent in the IL-12 KO mice. IL-18 mRNA was not increased after silica exposure. The expression of IL-15 (an important driver for innate immunity, Natural Killer cell activation, and IFN-γ production) was abundant in air-exposed mice and was increased slightly in the lungs of mice with silicosis. The axis of IL-12 driving IFN-γ production is not essential for the full manifestations of silicosis in mice exposed to a crystobalite silica aerosol.