Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, 20089, Milan, Italy.
Nanomedicine. 2024 Jan;55:102719. doi: 10.1016/j.nano.2023.102719. Epub 2023 Nov 17.
Chronic inflammatory diseases are increasing in developed societies, thus new anti-inflammatory approaches are needed in the clinic. Synthetic peptides complexes can be designed to mimic the activity of anti-inflammatory mediators, in order to alleviate inflammation. Here, we evaluated the anti-inflammatory efficacy of tethered peptides mimicking the interleukin-1 receptor antagonist (IL-1Ra) and the heat-shock protein 70 (HSP70). We tested their biocompatibility and anti-inflammatory activity in vitro in primary human monocytes and differentiated macrophages activated with two different stimuli: the TLR agonists (LPS + IFN-γ) or Pam3CSK4. Our results demonstrate that IL-1Ra and HSP70 synthetic peptides present a satisfactory biocompatible profile and significantly inhibit the secretion of several pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNFα). We further confirmed their anti-inflammatory activity when peptides were coated on a biocompatible material commonly employed in surgical implants. Overall, our findings support the potential use of IL-1Ra and HSP70 synthetic peptides for the treatment of inflammatory conditions.
慢性炎症性疾病在发达社会中日益增多,因此临床上需要新的抗炎方法。合成肽复合物可以设计为模拟抗炎介质的活性,以减轻炎症。在这里,我们评估了模拟白细胞介素 1 受体拮抗剂 (IL-1Ra) 和热休克蛋白 70 (HSP70) 的连接肽的抗炎功效。我们测试了它们在体外原代人单核细胞和用两种不同刺激物激活的分化巨噬细胞中的生物相容性和抗炎活性:TLR 激动剂(LPS+IFN-γ)或 Pam3CSK4。我们的结果表明,IL-1Ra 和 HSP70 合成肽具有令人满意的生物相容性特征,并显著抑制几种促炎细胞因子(IL-6、IL-8、IL-1β 和 TNFα)的分泌。当肽涂覆在手术植入物中常用的生物相容材料上时,我们进一步证实了它们的抗炎活性。总的来说,我们的研究结果支持使用 IL-1Ra 和 HSP70 合成肽治疗炎症性疾病。