Department of Immunology, Rappaport Faculty of Medicine, Technion and Rambam Medical Center, Haifa, Israel.
J Physiol Pharmacol. 2009 Nov;60 Suppl 5:81-6.
Cigarette smoking (CS) is associated with a variety of human pathologies including cardiovascular disease and cancer. Human monocytes are prevalent in oral and respiratory mucosa and may be affected by exposure to CS, which induces oxidative stress. As a result, up-regulation of nuclear factor-kappaB (NF-kappaB) may occur. Our aims were to analyze a possible regulatory effect of CS on NF-kappaB activity in human monocytes. Human monocyte cell lines were exposed to CS in vitro. Our findings show that in vitro exposure to CS did not affect viability of human monocytes and was associated with increased production and secretion of IL-8 and up-regulation of certain C-C chemokines. Inhibition of NF-kappaB with curcumin or parthenolide resulted in a decrease of IL-8 secretion. CS also impaired the differentiation of monocytes. However, induced secretion of IL-8 from differentiated monocytes was not impaired. Our results indicate that exposure to CS stimulates pro-inflammatory activity of human monocytes through the activation of NF-kappaB pathway and also interferes with monocyte differentiation, which could play a role in the carcinogenic effects of cigarette smoking.
吸烟与多种人类疾病有关，包括心血管疾病和癌症。人类单核细胞普遍存在于口腔和呼吸道黏膜中，可能会受到吸烟暴露的影响，吸烟会引起氧化应激。结果，核因子-κB（NF-κB）的上调可能发生。我们的目的是分析 CS 对人类单核细胞 NF-κB 活性的可能调节作用。体外培养的人单核细胞系暴露于 CS 中。我们的研究结果表明，体外暴露于 CS 不会影响人类单核细胞的活力，并与白细胞介素-8（IL-8）的产生和分泌增加以及某些 C-C 趋化因子的上调有关。用姜黄素或小白菊内酯抑制 NF-κB 会导致 IL-8 分泌减少。CS 还损害单核细胞的分化。然而，诱导分化的单核细胞分泌 IL-8 不受损害。我们的结果表明，暴露于 CS 通过激活 NF-κB 途径刺激人类单核细胞的促炎活性，并且还干扰单核细胞分化，这可能在吸烟的致癌作用中起作用。
