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白细胞介素-1β和肿瘤坏死因子α通过类风湿性关节炎滑膜成纤维细胞诱导粒细胞-巨噬细胞集落刺激因子表达来促进单核细胞活力。

IL-1β and TNFα promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial fibroblasts.

作者信息

Darrieutort-Laffite Christelle, Boutet Marie-Astrid, Chatelais Mathias, Brion Régis, Blanchard Frédéric, Heymann Dominique, Le Goff Benoit

机构信息

INSERM, UMR 957, 44035 Nantes, France ; Rheumatology Unit, Nantes University Hospital, 44093 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.

INSERM, UMR 957, 44035 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.

出版信息

Mediators Inflamm. 2014;2014:241840. doi: 10.1155/2014/241840. Epub 2014 Nov 17.

Abstract

BACKGROUND

Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype.

METHODS

SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry.

RESULTS

Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone (P < 0.001). This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF (P < 0.001). Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype.

CONCLUSION

Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization.

摘要

背景

巨噬细胞和滑膜成纤维细胞(SF)是类风湿关节炎(RA)发病机制中涉及的两种主要细胞。SF可能是驱动巨噬细胞存活和激活的细胞因子和生长因子的来源。在此,我们研究了SF对单核细胞活力和表型的影响。

方法

从RA患者的滑膜组织中分离出SF,从健康供体的外周血中分离出CD14+细胞。在有或无TNFα或IL-1β刺激的情况下培养24小时后收集SF条件培养基。通过流式细胞术研究巨噬细胞极化。

结果

与单独在培养基中培养的CD14+细胞相比,SF条件培养基使单核细胞活力显著提高了60%(P < 0.001)。使用IL-1β和TNFα刺激的SF的条件培养基可增强这种作用。当将GM-CSF阻断抗体添加到IL-1β和TNFα刺激的SF的条件培养基中时(P < 0.001),GM-CSF能显著降低单核细胞活力30%,而M-CSF和IL34阻断抗体则不能。最后,在SF条件培养基存在下培养的单核细胞未表现出特定的M1或M2表型。

结论

总体而言,用促炎细胞因子(IL-1β和TNFα)刺激的类风湿关节炎滑膜成纤维细胞通过GM-CSF促进单核细胞活力,但不诱导特定的巨噬细胞极化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce9d/4251793/e76cd4510a77/MI2014-241840.001.jpg

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