Exposure to Multi-Wall Carbon Nanotubes Promotes Fibrous Proliferation by Production of Matrix Metalloproteinase-12 via NF-κB Activation in Chronic Peritonitis.
Exposure to Multi-Wall Carbon Nanotubes Promotes Fibrous Proliferation by Production of Matrix Metalloproteinase-12 via NF-κB Activation in Chronic Peritonitis.
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DOI：
10.1016/j.ajpath.2022.07.009
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发表时间：
2022-08
期刊：
影响因子：
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通讯作者：
Takaaki Tsunematsu;R. Arakaki;Mami Sato;M. Saito;Kunihiro Otsuka;Yusuke Furukawa;Y. Taquahashi;J. Kanno;N. Ishimaru
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文献类型：
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作者：
Takaaki Tsunematsu;R. Arakaki;Mami Sato;M. Saito;Kunihiro Otsuka;Yusuke Furukawa;Y. Taquahashi;J. Kanno;N. Ishimaru
纳米材料，如碳纳米管（CNTs）对免疫系统的毒理学作用已经被很好地理解。然而，长期暴露于碳纳米管与慢性炎症之间的确切关系尚不清楚。本研究采用高分散效率的Taquann法处理多壁CNTs，腹腔注射建立小鼠慢性腹膜炎模型。在注射taquanan治疗的多壁碳纳米管（T-CNT）小鼠中观察到慢性腹膜炎伴纤维化，但在注射taquanan治疗的二氧化钛小鼠中没有观察到。体外实验表明，T-CNT可上调巨噬细胞的基质金属蛋白酶-12 (MMP-12)，增强成纤维细胞的活化和成纤维细胞中促纤维化分子的表达。此外，T-CNT诱导的腹膜炎降低了NF-κ b1−/−小鼠中MMP-12的表达，表明产生MMP-12的巨噬细胞通过NF-κB活化在T-CNT暴露引起的慢性炎症中起关键作用。本研究结果可能有助于了解纳米材料的分子毒性和慢性炎症。
The toxicologic effects of nanomaterials, such as carbon nanotubes (CNTs), on the immune system are understood well. However, the precise relationship between long-term exposure to CNTs and chronic inflammation remains unclear. In this study, a mouse model of chronic peritonitis was established using i.p. injection of multiwalled CNTs treated by the Taquann method with high dispersion efficiency. Chronic peritonitis with fibrosis was observed in Taquann-treated multiwalled CNT (T-CNT)–injected mice, but not in Taquann-treated titanium dioxide–injected mice.In vivoandin vitroexperiments showed that matrix metalloproteinase-12 (MMP-12) of macrophages was up-regulated by T-CNT to enhance fibroblast activation and profibrotic molecule expression in fibroblasts. In addition, T-CNT–induced peritonitis reduced MMP-12 expression inNfκb1−/−mice, suggesting that MMP-12–producing macrophages play a key role in chronic inflammation due to T-CNT exposure through NF-κB activation. The results of this study could be helpful in understanding the molecular toxicity of nanomaterial and chronic inflammation.