Trepicchio W L, Wang L, Bozza M, Dorner A J
Preclinical Molecular and Cellular Biology, Genetics Institute, Andover, MA 01810, USA.
J Immunol. 1997 Dec 1;159(11):5661-70.
Recombinant human IL-11 (rhIL-11) is an anti-inflammatory cytokine that can reduce the production of inflammatory mediators such as TNF-alpha, IL-1beta, IL-12, IL-6, and nitric oxide. Inhibition of proinflammatory cytokine production from activated macrophages was associated with a reduction in the levels of LPS-induced TNF-alpha, IL-1beta, IL-6, and IL-12 p40 mRNA. Analysis of rhIL-11 effects on transcription factors that activate proinflammatory cytokines demonstrated that the level of LPS-induced NF-kappaB binding activity in the nucleus of rhIL-11-treated peritoneal macrophages was significantly reduced. The block to NF-kappaB nuclear translocation correlated with the ability of rhIL-11 to maintain or increase protein levels of the inhibitors of NF-kappaB, IkappaB-alpha, and IkappaB-beta following LPS treatment. Furthermore, rhIL-11-treatment of LPS macrophages resulted in significant elevation of IkappaB-alpha and IkappaB-beta mRNA levels. These results suggest that the anti-inflammatory activity of rhIL-11 is mediated in part by inhibition of NF-kappaB-dependent transcriptional activation. Furthermore, these studies demonstrate for the first time the regulation of IkappaB-beta by an anti-inflammatory cytokine. Given the finding that inappropriate activation of NF-kappaB contributes to multiple inflammatory conditions, the ability of rhIL-11 to inhibit the binding activity of this pleiotropic transcription factor indicates that rhIL-11 has therapeutic potential in a wide range of diseases.
重组人白细胞介素-11（rhIL-11）是一种抗炎细胞因子，可减少炎性介质如肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-12、白细胞介素-6和一氧化氮的产生。活化巨噬细胞促炎细胞因子产生的抑制与脂多糖诱导的肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6和白细胞介素-12 p40 mRNA水平的降低相关。对rhIL-11对激活促炎细胞因子的转录因子的作用分析表明，rhIL-11处理的腹膜巨噬细胞核中脂多糖诱导的核因子-κB结合活性水平显著降低。核因子-κB核转位的阻断与rhIL-11在脂多糖处理后维持或增加核因子-κB抑制剂IκB-α和IκB-β蛋白水平的能力相关。此外，rhIL-11处理脂多糖巨噬细胞导致IκB-α和IκB-β mRNA水平显著升高。这些结果表明，rhIL-11的抗炎活性部分是通过抑制核因子-κB依赖性转录激活介导的。此外，这些研究首次证明了抗炎细胞因子对IκB-β的调节作用。鉴于核因子-κB的不适当激活与多种炎症状态有关，rhIL-11抑制这种多效性转录因子结合活性的能力表明rhIL-11在多种疾病中具有治疗潜力。
