Schlichter Kadosh Yael, Muthuraman Subramani, Kushmaro Ariel, Kumar Rajendran Saravana, Gopas Jacob
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Department of Chemistry, Vellore Institute of Technology, Chennai Campus, Chennai 600127, Tamilnadu, India.
J Immunol Res. 2025 Jan 8;2025:9915695. doi: 10.1155/jimr/9915695. eCollection 2025.
Inflammation is a critical response of the immune system to infection or injury, serving to repair and restore tissue homeostasis. While acute inflammation generally protects against harmful stimuli, prolonged and chronic inflammation have detrimental effects and disrupts tissue homeostasis. Due to the complex and multifactorial etiology of chronic inflammation, effective treatment remains elusive. We found that piperlongumine (PL)-18, a di-hydroxy derivative of PL from long pepper, inhibits the nuclear factor kappa B (NF-B), a master transcription factor of numerous components of the inflammatory response. NF-B was inhibited by PL-18 in two human cell-lines, L428 and A549, by preventing the nuclear translocation of p65 NF-B. We also found that IB kinase (IKK) was degraded in the presence of PL-18. Furthermore, PL-18 inhibited the production of proinflammatory cytokines expressed by L428, a cell line with a constitutive active NF-B. Altogether, our results suggest that PL-18 is a molecule of interest to be further developed to treat persistent infections with severe inflammation.
炎症是免疫系统对感染或损伤的关键反应，有助于修复和恢复组织稳态。虽然急性炎症通常能抵御有害刺激，但长期的慢性炎症具有有害影响并会破坏组织稳态。由于慢性炎症的病因复杂且涉及多因素，有效的治疗方法仍然难以捉摸。我们发现，荜茇明（PL）-18，一种来自荜茇的PL的二羟基衍生物，可抑制核因子κB（NF-κB），这是炎症反应众多成分的主要转录因子。在两种人类细胞系L428和A549中，PL-18通过阻止p65 NF-κB的核转位来抑制NF-κB。我们还发现，在PL-18存在的情况下，IκB激酶（IKK）会被降解。此外，PL-18抑制了L428（一种具有组成型活性NF-κB的细胞系）表达的促炎细胞因子的产生。总之，我们的结果表明，PL-18是一种值得进一步开发用于治疗伴有严重炎症的持续性感染的分子。
