白介素-1β诱导的牙髓细胞细胞间黏附分子-1 和白细胞介素-8 的表达/分泌受 IRAK 和 p38 的差异调节。
IL-1β-induced ICAM-1 and IL-8 expression/secretion of dental pulp cells is differentially regulated by IRAK and p38.
机构信息
Chang Gung University of Science and Technology, Kwei-Shan, Taoyuan, Taiwan; Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan.
Department of Dentistry, Tao-Yuan General Hospital, Ministry of Health and Welfare, Taoyuan City, Taiwan; Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taiwan.
出版信息
J Formos Med Assoc. 2019 Aug;118(8):1247-1254. doi: 10.1016/j.jfma.2018.11.015. Epub 2018 Dec 14.
BACKGROUND/PURPOSE: Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine involved in the acute and chronic inflammatory processes of dental pulp. Intercellular adhesion molecule-1 (ICAM-1) and IL-8 are two major inflammatory mediators. However, the role of interleukin-1 receptor-associated kinases (IRAKs) signaling pathways in responsible for the inflammatory effects of IL-1β on dental pulp cells is not clear.
METHODS
Cultured human dental pulp cells were exposed to IL-1β with/without pretreatment and co-incubation with IRAK1/4 inhibitor or SB203580 (p38 inhibitor). IRAK-1 phosphorylation was evaluated by immunno fluorescent staining. The protein expression of ICAM-1 and IL-8 were tested by western blotting. The secretion of soluble ICAM-1 (sICAM-1) and IL-8 was measured by enzyme-linked immunosorbant assay (ELISA).
RESULTS
IL-1β stimulated IRAK-1 phosphorylation of pulp cells within 120 min of exposure. IRAK1/4 inhibitor attenuated the IL-1β-induced ICAM-1, but not IL-8 protein expression. IRAK1/4 inhibitor also prevented the IL-1β-induced sICAM-1, but not IL-8 secretion. SB203580 showed little effect on IL-1β-induced sICAM-1 secretion, but effectively inhibited its induction of IL-8 secretion in pulp cells.
CONCLUSION
The Results reveal the important role of IL-1β in pulpal inflammatory responses via stimulation of IL-8 and ICAM-1 expression and secretion. Moreover, IL-1β-induced effects on IL-8 and ICAM-1 are differentially regulated by IRAK1/4 and p38 signaling in dental pulp cells. Blocking of IRAKs and p38 signaling may have potential to control inflammation of dental pulp in the future.
背景/目的：白细胞介素 1β（IL-1β）是一种参与牙髓急性和慢性炎症过程的促炎细胞因子。细胞间黏附分子-1（ICAM-1）和白细胞介素-8（IL-8）是两种主要的炎症介质。然而，白细胞介素-1受体相关激酶（IRAKs）信号通路在 IL-1β对牙髓细胞炎症作用中的作用尚不清楚。
方法
将培养的人牙髓细胞暴露于 IL-1β中，有/无预处理和共孵育 IRAK1/4 抑制剂或 SB203580（p38 抑制剂）。通过免疫荧光染色评估 IRAK-1 磷酸化。通过 Western blot 检测 ICAM-1 和 IL-8 的蛋白表达。通过酶联免疫吸附试验（ELISA）测量可溶性 ICAM-1（sICAM-1）和 IL-8 的分泌。
结果
IL-1β 刺激牙髓细胞 IRAK-1 磷酸化在暴露后 120 分钟内。IRAK1/4 抑制剂减弱了 IL-1β诱导的 ICAM-1，但不影响 IL-8 蛋白表达。IRAK1/4 抑制剂还阻止了 IL-1β诱导的 sICAM-1，但不影响 IL-8 分泌。SB203580 对 IL-1β诱导的 sICAM-1 分泌影响不大，但有效抑制了其对牙髓细胞中 IL-8 分泌的诱导。
结论
结果表明，IL-1β 通过刺激 IL-8 和 ICAM-1 的表达和分泌在牙髓炎症反应中发挥重要作用。此外，IL-1β 对 IL-8 和 ICAM-1 的诱导作用通过 IRAK1/4 和 p38 信号通路在牙髓细胞中差异调节。阻断 IRAKs 和 p38 信号通路可能有助于控制未来牙髓的炎症。
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