Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Toxicol Appl Pharmacol. 2014 Sep 1;279(2):211-9. doi: 10.1016/j.taap.2014.06.001. Epub 2014 Jun 10.
Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1h or 5h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5h), which was increased by nicotine but suppressed by other components of STE. Within 2h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research.
皮肤成纤维细胞构成了抵抗伤口的第一道防线，而烟草制品直接接触口腔。将培养的人真皮成纤维细胞暴露于无烟烟草提取物（STE）、烟草烟雾中的总颗粒物（TPM）或尼古丁中，浓度与这些提取物中的浓度相当，持续 1 小时或 5 小时。使用 qRT-PCR 比较处理组与载体组之间特定途径基因的差异。在 1 小时时，TPM 显著抑制了 IL1α，而 STE 的抑制作用较小。1 小时时，烟草制品对 FOS 和 JUN 均无抑制作用。IL8、TNFα、VCAM1 和 NFκB1 在经过 5 小时的 STE 处理后被抑制，而 TPM 仅抑制 TNFα 和 NFκB1。在 1 小时时，TPM 增加了 IL10 和 TNFα 的分泌水平。基因如 ATF3（5 小时）的潜在混杂作用说明了尼古丁的潜在混杂作用，尼古丁增加了 ATF3，但 STE 的其他成分则抑制了 ATF3。在 2 小时内，TPM 刺激了一氧化氮的产生，而 STE 和 TPM 都增加了活性氧。这些发现的生物学意义以及关于烟草制品制剂对真皮成纤维细胞影响的本文报道的基因表达变化的利用需要进一步研究。
