Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Innate Immun. 2009 Aug;15(4):217-24. doi: 10.1177/1753425909103738. Epub 2009 Jul 8.
The inhibitory effect of interleukin-10 (IL-10), an anti-inflammatory cytokine, on lipopolysaccharide (LPS)-induced IL-6 production was characterized by simultaneous stimulation of RAW 264.7 cells with LPS and IL-10. The presence of IL-10 significantly inhibited LPS-induced IL-6 production at a transcriptional level. The expression of IkappaB-zeta, which promotes IL-6 production, was induced in response to LPS and it was definitely suppressed in the presence of IL-10. Further, IL-10 inhibited LPS-induced NF-kappaB activation. A pharmacological inhibitor of NF-kappaB prevented LPS-induced IkappaB-zeta expression, suggesting that IL-10 might inhibit LPS-induced IkappaB-zeta expression via the inactivation of NF-kappaB. In LPS- and IL-10-stimulated cells, the expression of Bcl-3 that inhibits NF-kappaB activation was significantly augmented. Introduction of Bcl-3 siRNA abolished IL-10-mediated IkappaB-zeta inhibition. In the presence of Bcl-3, siRNA IL-10 failed to inhibit LPS-induced IL-6 production. Therefore, it was suggested that Bcl-3 induced by IL-10 might reduce LPS-induced IkappaB-zeta activity via inactivation of NF-kappaB and that reduced IkappaB-zeta activity failed to promote LPS-induced IL-6 production.
白细胞介素-10（IL-10）是一种抗炎细胞因子，其对脂多糖（LPS）诱导的 IL-6 产生的抑制作用通过同时刺激 RAW 264.7 细胞来表征。IL-10 的存在显著抑制了 LPS 诱导的 IL-6 在转录水平上的产生。响应 LPS 诱导表达了促进 IL-6 产生的 IkappaB-zeta，而在存在 IL-10 的情况下其表达受到明显抑制。此外，IL-10 抑制 LPS 诱导的 NF-kappaB 激活。NF-kappaB 的药理学抑制剂可阻止 LPS 诱导的 IkappaB-zeta 表达，表明 IL-10 可能通过 NF-kappaB 的失活来抑制 LPS 诱导的 IkappaB-zeta 表达。在 LPS 和 IL-10 刺激的细胞中，抑制 NF-kappaB 激活的 Bcl-3 的表达明显增加。引入 Bcl-3 siRNA 可消除 IL-10 介导的 IkappaB-zeta 抑制。在 Bcl-3 存在的情况下，siRNA IL-10 未能抑制 LPS 诱导的 IL-6 产生。因此，据推测，IL-10 诱导的 Bcl-3 可能通过 NF-kappaB 的失活来降低 LPS 诱导的 IkappaB-zeta 活性，而降低的 IkappaB-zeta 活性未能促进 LPS 诱导的 IL-6 产生。
