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城市颗粒物对培养的人鼻腔成纤维细胞的影响。

The effect of urban particulate matter on cultured human nasal fibroblasts.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Clinical Research Institute, Daejeon St. Mary's Hospital, Daejeon, Republic of Korea.

出版信息

Int Forum Allergy Rhinol. 2018 Sep;8(9):993-1000. doi: 10.1002/alr.22167. Epub 2018 Jul 6.

Abstract

BACKGROUND

Exposure to urban particulate matter (UPM) has been linked to aggravation of various health problems. Although the effects of UPM on the lower respiratory tract have been extensively studied, more research is required on the impact of UPM on the upper respiratory tract and the underlying mechanisms. Thus, we investigated the cytotoxic effects of UPM on cultured human nasal fibroblasts, the underlying signaling pathways involved, and changes in cytokine levels.

METHODS

Human turbinate tissue specimens were collected during partial turbinectomies performed on 6 patients, and then cultured. The effect of UPM on nasal fibroblast viability was explored. Real-time reverse transcription-polymerase chain reaction was used to measure the mRNA levels of genes encoding cytokines and chemokines (interleukin [IL]-4, IL-6, IL-8, and tumor necrosis factor-α) before and after 24 hours of UPM treatment. Enzyme-linked immunosorbent assays were employed to measure IL-6 and IL-8 levels. The status of the p38 and nuclear factor (NF)-κB signaling pathways was analyzed by Western blotting.

RESULTS

UPM reduced cell viability in a dose-dependent manner and increased IL-6 and IL-8 expression at both the mRNA and protein levels. UPM induced the phosphorylation of p38 and NF-κB p65; inhibitors of the actions of these proteins repressed phosphorylation and the expression of IL-6 and IL-8.

CONCLUSION

UPM induced IL-6 and IL-8 expression by fibroblasts via p38 and NF-κB classical signaling, suggesting that UPM can induce or aggravate allergic and/or chronic rhinitis.

摘要

背景

暴露于城市颗粒物(UPM)已被证明与多种健康问题的恶化有关。尽管 UPM 对下呼吸道的影响已经得到了广泛的研究,但仍需要更多的研究来了解 UPM 对上呼吸道的影响及其潜在机制。因此,我们研究了 UPM 对培养的人鼻腔成纤维细胞的细胞毒性作用、涉及的潜在信号通路以及细胞因子水平的变化。

方法

在 6 名患者进行部分鼻甲切除术期间采集人鼻甲组织标本,并进行培养。探讨 UPM 对鼻成纤维细胞活力的影响。采用实时逆转录聚合酶链反应检测 UPM 处理 24 小时前后编码细胞因子和趋化因子(白细胞介素[IL]-4、IL-6、IL-8 和肿瘤坏死因子-α)的基因的 mRNA 水平。采用酶联免疫吸附试验测定 IL-6 和 IL-8 水平。采用 Western blot 分析 p38 和核因子(NF)-κB 信号通路的状态。

结果

UPM 呈剂量依赖性降低细胞活力,并增加 IL-6 和 IL-8 在 mRNA 和蛋白水平的表达。UPM 诱导 p38 和 NF-κB p65 的磷酸化;这些蛋白的作用抑制剂抑制磷酸化和 IL-6 和 IL-8 的表达。

结论

UPM 通过 p38 和 NF-κB 经典信号通路诱导成纤维细胞表达 IL-6 和 IL-8,表明 UPM 可诱导或加重变应性和/或慢性鼻炎。

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