Ligi Daniela, Mosti Giovanni, Croce Lidia, Raffetto Joseph D, Mannello Ferdinando
Department of Biomolecular Sciences, Section of Clinical Biochemistry and Molecular Genetics, University "Carlo Bo", Urbino, Italy.
Department of Angiology, Barbantini Clinic, via del Calcio 2, 55100 Lucca, Italy.
Biochim Biophys Acta. 2016 Oct;1862(10):1964-74. doi: 10.1016/j.bbadis.2016.07.018. Epub 2016 Jul 28.
Venous leg ulcers (VLUs) produce wound fluid (WF), as a result of inflammatory processes within the wound. It is unclear if WF from different healing phases of VLU has a peculiar biochemical profile and how VLU microenvironment affects the wound healing mechanisms. This study was conducted to evaluate the cytokine/chemokine profiles in WF from distinct VLU phases, in WF- and LPS-stimulated monocytes and treated with glycosaminoglycan Sulodexide, a therapeutic option for VLU healing. WF and plasma were collected from patients with VLU during active inflammatory (Infl) and granulating (Gran) phases. Demographics, clinical characteristics and pain measurements were evaluated. WF, plasma, and THP-1 supernatants were analyzed for 27 inflammatory mediators by multiplex immunoassay. Our results demonstrated that: 1) pain was significantly increased in patients with Infl compared to Gran VLU; 2) cytokine profile of Infl WF was found to be statistically different from that Gran WF, as well significantly increased respect to plasma; 3) LPS- and WF-stimulation of THP-1 cells significantly increased the expression of several cytokines compared to untreated cells; 4) Sulodexide treatment of both LPS- and WF-stimulated THP-1 monocytes was able to significantly down-regulate the release of peculiar inflammatory mediators. Our study highlighted the importance to understand biomolecular processes underlying CVI when providing treatment for chronic VLU. Identification of inflammatory biomarkers in leg ulcer microenvironment, may provide useful tools for predicting healing outcome and developing targeted therapies.
由于伤口内的炎症过程，下肢静脉溃疡（VLU）会产生伤口渗出液（WF）。目前尚不清楚来自VLU不同愈合阶段的WF是否具有独特的生化特征，以及VLU微环境如何影响伤口愈合机制。本研究旨在评估来自VLU不同阶段的WF、经WF和脂多糖（LPS）刺激的单核细胞以及用糖胺聚糖舒洛地特（一种用于VLU愈合的治疗选择）处理后的细胞因子/趋化因子谱。在炎症活跃期（Infl）和肉芽形成期（Gran）从VLU患者中收集WF和血浆。评估人口统计学、临床特征和疼痛测量结果。通过多重免疫测定法分析WF、血浆和THP-1上清液中的27种炎症介质。我们的结果表明：1）与Gran VLU患者相比，Infl患者的疼痛明显增加；2）发现Infl WF的细胞因子谱与Gran WF在统计学上不同，并且相对于血浆也显著增加；3）与未处理的细胞相比，LPS和WF刺激THP-1细胞显著增加了几种细胞因子的表达；4）舒洛地特对LPS和WF刺激的THP-1单核细胞的处理能够显著下调特定炎症介质的释放。我们的研究强调了在为慢性VLU提供治疗时了解静脉慢性疾病（CVI）潜在生物分子过程的重要性。识别腿部溃疡微环境中的炎症生物标志物，可能为预测愈合结果和开发靶向治疗提供有用的工具。
