Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, Strada Le Grazie 8, I-37134 Verona, Italy.
San Rocco Clinic, Via Monsignor G.V. Moreni 95, I-25018 Montichari, Italy.
Int J Mol Sci. 2021 Sep 20;22(18):10133. doi: 10.3390/ijms221810133.
Oxygen-ozone (O-O) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines. The administration of O-O gas mixtures induced multiple effects on fibroblasts, depending on their activation state: in non-activated fibroblasts, O stimulated proliferation, formation of cell surface protrusions, antioxidant response, and IL-6 and TGF-β1 secretion, while in LPS-activated fibroblasts, O stimulated only antioxidant response and cytokines secretion. Therefore, the low O concentrations used in this study induced activation-like responses in non-activated fibroblasts, whereas in already activated fibroblasts, the cell protective capability was potentiated.
氧气-臭氧（O-O）治疗作为多种疾病的辅助治疗方法越来越受到重视；然而，低浓度 O 产生疗效的生物学机制需要进一步研究，以了解其对不同细胞类型可能产生的多种影响。在这项工作中，我们将注意力集中在成纤维细胞上，成纤维细胞作为普遍存在的连接细胞，在身体结构、组织常驻细胞的内稳态以及许多生理和病理过程中发挥作用。我们采用已建立的人成纤维细胞系作为体外模型，采用多模态方法探索细胞结构和功能特征的面板，结合了光和电子显微镜、Western blot 分析、实时定量聚合酶链反应和细胞因子的多重分析。O-O 气体混合物的给药对成纤维细胞产生了多种影响，具体取决于其激活状态：在非激活的成纤维细胞中，O 刺激增殖、细胞表面突起形成、抗氧化反应以及 IL-6 和 TGF-β1 的分泌，而在 LPS 激活的成纤维细胞中，O 仅刺激抗氧化反应和细胞因子的分泌。因此，本研究中使用的低 O 浓度在非激活的成纤维细胞中诱导类似激活的反应，而在已经激活的成纤维细胞中，则增强了细胞保护能力。
