College of Science, Health, Engineering and Education, Murdoch University, Perth, Western Australia, Australia.
College of Science, Health, Engineering and Education, Murdoch University, Perth, Western Australia, Australia; Telethon Kids Institute, Perth, Western Australia, Australia.
Exp Cell Res. 2020 Jun 15;391(2):112008. doi: 10.1016/j.yexcr.2020.112008. Epub 2020 Apr 15.
A positive feedback loop between inflammatory cytokines and alpha-adrenoceptors (α-AR) (a target of the sympathetic nervous system neurotransmitter norepinephrine) influences inflammatory responses in immune cells. This cross-talk between the sympathetic nervous system and immune system may play a role in promoting chronic inflammation. Emerging evidence shows that α-AR interact with inflammatory cytokines in keratinocytes, and this epidermal adrenergic signalling may contribute to skin inflammatory responses following injury, disease or stress. In this study, utilizing an in vitro approach, we hypothesized that α-AR interact in a positive feedback loop with inflammatory mediators in keratinocytes. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) was used to induce an inflammatory state in cultured keratinocytes. TNFα increased interleukin (IL)-1β, IL-6, IL-8 and nerve growth factor (NGF) production and gene expression levels of α-AR subtype B (α-AR). Additional stimulation of α-AR further increased IL-6 levels, while maintaining high levels of IL-8 and decreasing levels of IL-1β and NGF. Our results suggest that reciprocal influences between α-ARs and inflammatory cytokines may play a role in normal inflammatory responses. However, if unchecked, this cycle could contribute to pathology (e.g. chronic inflammatory diseases, chronic pain conditions, and stress-induced cancer progression).
炎症细胞因子与α-肾上腺素能受体（α-AR）（交感神经系统神经递质去甲肾上腺素的靶标）之间的正反馈循环影响免疫细胞中的炎症反应。交感神经系统和免疫系统之间的这种串扰可能在促进慢性炎症中发挥作用。新出现的证据表明，α-AR 与角质形成细胞中的炎症细胞因子相互作用，这种表皮肾上腺素能信号可能有助于损伤、疾病或应激后皮肤的炎症反应。在这项研究中，我们利用体外方法假设 α-AR 与角质形成细胞中的炎症介质以正反馈环相互作用。使用促炎细胞因子肿瘤坏死因子-α（TNFα）诱导培养的角质形成细胞中的炎症状态。TNFα增加白细胞介素（IL）-1β、IL-6、IL-8 和神经生长因子（NGF）的产生和 α-AR 亚型 B（α-AR）的基因表达水平。进一步刺激α-AR 进一步增加了 IL-6 的水平，同时保持了高水平的 IL-8，并降低了 IL-1β 和 NGF 的水平。我们的结果表明，α-AR 和炎症细胞因子之间的相互影响可能在正常炎症反应中发挥作用。然而，如果不受控制，这种循环可能导致病理学（例如慢性炎症性疾病、慢性疼痛状况和应激诱导的癌症进展）。
