Poulaki Smaragda, Kalantidou Aikaterini, Lapi Ioanna, Gravanis Achille, Venihaki Maria
Department of Clinical Chemistry, Medical School, University of Crete, 71500 Heraklion, Crete, Greece.
Department of Pediatrics, School of Medicine, University of Crete, 71500 Heraklion, Crete, Greece.
Int J Mol Sci. 2025 Jun 8;26(12):5498. doi: 10.3390/ijms26125498.
During tissue injury or infection, leukocytes are activated to produce proinflammatory mediators, which trigger the immune system to produce anti-inflammatory and analgesic molecules. Our previous studies provide evidence that synthetic microneurotrophins, like BNN27, exert significant analgesic and anti-inflammatory effects during Complete Freund's Adjuvant (CFA)-induced inflammation and pain. Thus, the aim of the present study was to examine if the effect of BNN27 on inflammatory pain is mediated at least in part by activation of T-lymphocytes. For this purpose, six hours following the injection of CFA, spleens were harvested in PBS and lymphocytes were collected and placed in medium containing concanavalin-A and IL-2 to prompt T-lymphocyte proliferation and differentiation. Cells were then treated with BNN27 at different concentrations and the media and cells were collected for ELISA and PCR assays. The proliferation rate of T-cells was also examined using the MTT assay. Our results showed that BNN27 significantly increased the proliferation of T-lymphocytes. In addition, BNN27 significantly decreased IL-6 and TNF-α protein levels, while it increased the mRNA expression of μ-opioid receptor and opioid peptides PENK and POMC at different time points. Our data demonstrate considerable anti-inflammatory and analgesic effects of BNN27, making it a promising molecule for inflammation and pain management.
在组织损伤或感染期间,白细胞被激活以产生促炎介质,这些介质触发免疫系统产生抗炎和镇痛分子。我们之前的研究提供了证据,表明合成的微神经营养因子,如BNN27,在完全弗氏佐剂(CFA)诱导的炎症和疼痛过程中发挥显著的镇痛和抗炎作用。因此,本研究的目的是检验BNN27对炎性疼痛的作用是否至少部分是由T淋巴细胞的激活介导的。为此,在注射CFA六小时后,在PBS中采集脾脏,收集淋巴细胞并置于含有伴刀豆球蛋白A和白细胞介素-2的培养基中,以促进T淋巴细胞的增殖和分化。然后用不同浓度的BNN27处理细胞,并收集培养基和细胞用于ELISA和PCR分析。还使用MTT法检测T细胞的增殖率。我们的结果表明,BNN27显著增加了T淋巴细胞的增殖。此外,BNN27在不同时间点显著降低了白细胞介素-6和肿瘤坏死因子-α的蛋白水平,同时增加了μ-阿片受体以及阿片肽PENK和POMC的mRNA表达。我们的数据证明了BNN27具有显著的抗炎和镇痛作用,使其成为用于炎症和疼痛管理的有前景的分子。