Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
J Dermatol Sci. 2014 Feb;73(2):135-41. doi: 10.1016/j.jdermsci.2013.10.006. Epub 2013 Oct 29.
The functions of lymphatic vessels are to drain the protein-rich lymph from the extracellular space, to maintain normal tissue pressure, and to mediate the immune response, particularly in inflammatory conditions.
To evaluate the function of the vascular endothelial growth factor (VEGF)-C/VEGF receptor (VEGFR)-3 signaling pathway in chronic skin inflammation.
We used adenovirus-mediated VEGF-C or VEGFR3-immunoglobulin (Ig) production and investigated the effects of VEGF-C/VEGFR3 signaling on the resolution of inflammation using the experimental chronic contact hypersensitivity (CHS) reaction mouse model.
VEGF-C gene transfer promoted significant reduction of ear swelling and ear weight in CHS reaction-induced skin inflammation. Although, there was no significant difference in the number of lymphatic vessels, the number of infiltrating CD11b-positive inflammatory cells was significantly reduced in the VEGF-C group, which suggested that VEGF-C upregulated the drainage of interstitial fluid and inflammatory cells via lymphatic vessels. Furthermore, blockade of VEGFR3 expression resulted in a significant delay in the recovery from CHS reaction-induced skin inflammation. Lymphatic vessel size was enlarged and a significant increase of infiltrating CD11b inflammatory cells was observed in mice with VEGFR3-Ig gene transfer compared to control mice. These results suggested that blockade of VEGFR3 inhibited the drainage function of the lymphatic system.
This study provides evidence that VEGF-C/VEGFR3 signaling plays an important role in the resolution of skin inflammation; the regulation of lymphatic function may have a great therapeutic potential in inflammatory skin diseases.
淋巴管的功能是从细胞外空间排出富含蛋白质的淋巴液，维持正常的组织压力，并介导免疫反应，特别是在炎症情况下。
评估血管内皮生长因子（VEGF）-C/VEGF 受体（VEGFR）-3 信号通路在慢性皮肤炎症中的作用。
我们使用腺病毒介导的 VEGF-C 或 VEGFR3-免疫球蛋白（Ig）产生，并使用实验性慢性接触超敏反应（CHS）反应小鼠模型研究 VEGF-C/VEGFR3 信号对炎症消退的影响。
VEGF-C 基因转移促进了 CHS 反应诱导的皮肤炎症中耳朵肿胀和耳朵重量的显著减少。虽然淋巴管数量没有显著差异，但 VEGF-C 组浸润的 CD11b 阳性炎症细胞数量明显减少，这表明 VEGF-C 通过淋巴管上调了间质液和炎症细胞的引流。此外，阻断 VEGFR3 表达导致 CHS 反应诱导的皮肤炎症恢复明显延迟。与对照小鼠相比，VEGFR3-Ig 基因转移的小鼠淋巴管增大，浸润的 CD11b 炎症细胞明显增加。这些结果表明，阻断 VEGFR3 抑制了淋巴管的引流功能。
本研究提供的证据表明，VEGF-C/VEGFR3 信号在皮肤炎症的消退中起着重要作用；调节淋巴管功能在炎症性皮肤病中可能具有很大的治疗潜力。
