Department of Biopharmaceutical Sciences, Laboratory of Microbiology, Gifu Pharmaceutical University, Gifu, Japan.
Innate Immun. 2012 Jun;18(3):429-37. doi: 10.1177/1753425911416022. Epub 2011 Sep 26.
The effect of 10-hydroxy-trans-2-decenoic acid (10H2DA), a major fatty acid component of royal jelly, was investigated on LPS-induced cytokine production in murine macrophage cell line, RAW264 cells. 10H2DA inhibited LPS-induced IL-6 production dose-dependently, but did not inhibit TNF-α production. 10H2DA inhibited LPS-induced NF-κB activation in a dose-dependent fashion. In addition, NF-κB activation induced by over-expression of either MyD88 or Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) was also inhibited by 10H2DA. Degradation of IκB-α and phosphorylation of IκB kinase-α were not inhibited by 10H2DA. On the other hand, reduction of LPS-induced IκB-ζ expression was discovered. Production of lipocalin-2 and granulocyte colony-stimulating factor (G-CSF), which is dependent on IκB-ζ, was also inhibited by 10H2DA, whereas that of IκB-ζ-independent cytokines/chemokines, such as IFN-β, murine monocyte chemotactic protein-1 (JE), macrophage inflammatory protein (MIP)-1α and MIP-2, was not. Together, 10H2DA specifically inhibited LPS-induced IκB-ζ expression, followed by inhibition of IκB-ζ-dependent gene production. These results suggest that 10H2DA is one of the components of royal jelly to show anti-inflammatory effects and could be a therapeutic drug candidate for inflammatory and autoimmune diseases associated with IκB-ζ and IL-6 production.
10-羟基-反-2-癸烯酸（10H2DA）是蜂王浆的主要脂肪酸成分之一，其对脂多糖（LPS）诱导的鼠源巨噬细胞系 RAW264 细胞细胞因子产生的影响进行了研究。10H2DA 呈剂量依赖性地抑制 LPS 诱导的 IL-6 产生，但不抑制 TNF-α 产生。10H2DA 呈剂量依赖性地抑制 LPS 诱导的 NF-κB 活化。此外，MyD88 或 Toll/IL-1 受体结构域包含衔接诱导 IFN-β（TRIF）的过表达诱导的 NF-κB 活化也被 10H2DA 抑制。IκB-α 的降解和 IκB 激酶-α的磷酸化不受 10H2DA 抑制。另一方面，发现 LPS 诱导的 IκB-ζ 表达减少。脂联素-2 和粒细胞集落刺激因子（G-CSF）的产生（依赖于 IκB-ζ）也被 10H2DA 抑制，而 IκB-ζ 非依赖性细胞因子/趋化因子，如 IFN-β、鼠单核细胞趋化蛋白-1（JE）、巨噬细胞炎症蛋白（MIP）-1α 和 MIP-2 的产生不受 10H2DA 抑制。总之，10H2DA 特异性抑制 LPS 诱导的 IκB-ζ 表达，随后抑制 IκB-ζ 依赖性基因产物的产生。这些结果表明 10H2DA 是蜂王浆中具有抗炎作用的成分之一，可能是与 IκB-ζ 和 IL-6 产生相关的炎症和自身免疫性疾病的治疗药物候选物。
