Chovanova Lucia, Vlcek Miroslav, Krskova Katarina, Penesova Adela, Radikova Zofia, Rovensky Jozef, Cholujova Dana, Sedlak Jan, Imrich Richard
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Gen Physiol Biophys. 2013 Sep;32(3):395-404. doi: 10.4149/gpb_2013043. Epub 2013 Jul 2.
TLR4-mediated inflammatory responses are important for innate immune functions, thus their alterations may participate in the pathogenesis of rheumatoid arthritis (RA). Cortisol is one of the most potent immunomodulatory hormones involved in control of inflammation. In this study, we analyzed TLR4-mediated responses and cortisol effects on the process in peripheral blood mononuclear cells (PBMC) from RA patients. Lipopolysaccharide-stimulated PBMC from 23 female patients and 15 healthy controls were cultured in the presence or absence of cortisol (1 μM) for 24 h. A panel of 17 inflammatory cytokines was analyzed in the cell culture supernatants. Higher (p < 0.05) concentrations of IL-6, IL-17 and MCP-1 were found in lipopolysaccharide-stimulated PBMC from RA patients compared to controls. After normalization of stimulated cytokine secretion to unstimulated cells, a significantly higher (p < 0.05) IL-6 and G-CSF production was found in RA PBMC. Cortisol induced stronger (p < 0.05) suppression of lipopolysaccharide-stimulated secretion of IL-1β, IL-6, IL-17 and G-CSF in RA group compared to controls. The observed higher production of the key inflammatory cytokines by RA PBMC to lipopolysaccharide stimulation supports involvement of TLR4-mediated processes in RA pathogenesis. The higher sensitivity of LPS-stimulated RA PBMC to immunosuppressive effects of cortisol may reflect adaptive processes to chronic inflammation.
Toll样受体4（TLR4）介导的炎症反应对先天免疫功能很重要，因此其改变可能参与类风湿性关节炎（RA）的发病机制。皮质醇是参与炎症控制的最有效的免疫调节激素之一。在本研究中，我们分析了TLR4介导的反应以及皮质醇对RA患者外周血单核细胞（PBMC）中该过程的影响。来自23名女性患者和15名健康对照的脂多糖刺激的PBMC在有或没有皮质醇（1μM）的情况下培养24小时。在细胞培养上清液中分析了一组17种炎性细胞因子。与对照组相比，在RA患者的脂多糖刺激的PBMC中发现IL-6、IL-17和MCP-1的浓度更高（p<0.05）。在将刺激的细胞因子分泌与未刺激的细胞进行标准化后，在RA PBMC中发现IL-6和粒细胞集落刺激因子（G-CSF）的产生明显更高（p<0.05）。与对照组相比，皮质醇在RA组中对脂多糖刺激的IL-1β、IL-6、IL-17和G-CSF分泌的抑制作用更强（p<0.05）。观察到RA PBMC对脂多糖刺激产生的关键炎性细胞因子更高，这支持了TLR4介导的过程参与RA发病机制。脂多糖刺激的RA PBMC对皮质醇免疫抑制作用的更高敏感性可能反映了对慢性炎症的适应性过程。
