The IκB kinase (IKK) complex plays a vital role in regulating the NF-κB activation. Aberrant NF-κB activation is involved in various inflammatory diseases. Thus, targeting IKK activation is an ideal therapeutic strategy to cure and prevent inflammatory diseases related to NF-κB activation. In a previous study, we demonstrated that IKK-interacting protein (IKIP) inhibits the phosphorylation of IKKα/β and the activation of NF-κB through disruption of the formation of IKK complex. In this study, we identified a 15-aa peptide derived from mouse IKIP (46–60 aa of IKIP), which specifically suppressed IKK activation and NF-κB targeted gene expression via disrupting the association of IKKβ and NEMO. Importantly, administration of the peptide reduced LPS-induced acute inflammation and attenuated Zymosan-induced acute arthritis in mice. These findings suggest that this IKIP peptide may be a promising therapeutic reagent in the prevention and treatment of inflammatory diseases.

IκB 激酶 (IKK) 复合物在调节 NF-κB 活化中起着至关重要的作用。异常的 NF-κB 激活与各种炎症疾病有关。因此，靶向 IKK 激活是治愈和预防与 NF-κB 激活相关的炎症性疾病的理想治疗策略。在之前的一项研究中，我们证明 IKK 相互作用蛋白 (IKIP) 通过破坏 IKK 复合物的形成来抑制 IKKα/β 的磷酸化和 NF-κB 的激活。在这项研究中，我们鉴定了一种源自小鼠 IKIP（IKIP 的 46-60 aa）的 15-aa 肽，它通过破坏 IKKβ 和 NEMO 的关联来特异性抑制 IKK 激活和 NF-κB 靶向基因表达。重要的是，该肽的给药减少了 LPS 诱导的急性炎症并减轻了酵母多糖诱导的小鼠急性关节炎。