Blocking IL-22, a potential treatment strategy for adenomyosis by inhibiting crosstalk between vascular endothelial and endometrial stromal cells.
Blocking IL-22, a potential treatment strategy for adenomyosis by inhibiting crosstalk between vascular endothelial and endometrial stromal cells.
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阻断 IL-22，这是一种通过抑制血管内皮细胞和子宫内膜基质细胞之间的串扰来治疗子宫腺肌症的潜在治疗策略。
DOI：
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发表时间：
2015-10
影响因子：
2.2
通讯作者：
Li Ming-Qing
中科院分区：
文献类型：
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作者：
Shang Wen-Qing;Yu Jia-Jun;Zhu Lei;Zhou Wen-Jie;Chang Kai-Kai;Wang Qing;Li Ming-Qing
我们的前期工作已经证明白细胞介素-22（IL-22）以自分泌的方式增强子宫腺肌病子宫内膜间质细胞（ESCs）的侵袭力。在本研究中，我们进一步研究了IL-22是否介导血管内皮细胞（VECs）和ESCs之间的体外串扰。我们发现子宫腺肌病患者异位病灶的血管内皮细胞高度表达IL-22受体IL-22 R1和IL-10 R2。重组人IL-22（rhIL-22）和来自ESC的IL-22均增加人脐静脉内皮细胞（HUVECs）上IL-22 R1和IL-10 R2的表达。rhIL-22处理可提高HUVECs活力，但不影响HUVECs凋亡。相反，抗人IL-22中和抗体（α-IL-22）抑制由ESC上清液诱导的HUVECs活力。rhIL-22或ESCs刺激HUVECs可上调CD 105表达，促进血管生成，α-IL-22可逆转ESCs的上述作用。与未处理的HUVECs相比，经rh-IL-22或ESCs培养的HUVECs可进一步上调Ki-67和增殖细胞核抗原（PCNA）的表达，下调Fas配体（FasL）的表达。然而，由ESC-教育的HUVECs诱导的这些作用被α-IL-22抑制。结果表明，ESC来源的IL-22可促进HUVEC的IL-22受体表达，增强HUVEC的活力、活化和血管生成。反过来，受过训练的HUVEC可能进一步刺激ESC的增殖并限制其凋亡。子宫腺肌病的发生发展可能与其整体效应有关。阻断IL-22可以干扰IL-22介导的ESC和VEC之间的相互作用，提示阻断IL-22可能是子宫腺肌病的潜在治疗策略。
Our previous work has demonstrated that interleukin-22 (IL-22) enhances the invasiveness of endometrial stromal cells (ESCs) of adenomyosis in an autocrine manner. In the present study, we further investigated whether IL-22 mediated crosstalk between vascular endothelial cells (VECs) and ESCs in vitro. Here we found that VECs in ectopic lesion from women with adenomyosis highly expressed IL-22 receptors IL-22R1 and IL-10R2. Both recombinant human IL-22 (rhIL-22) and IL-22 from ESCs increased IL-22R1 and IL-10R2 expression on human umbilical vein endothelial cells (HUVECs). Treatment with rhIL-22 led to an elevation of HUVECs viability, but did not influence HUVECs apoptosis. In contrast, anti-human IL-22 neutralizing antibody (α-IL-22) inhibited HUVECs viability induced by supernatants of ESCs. Stimulation with rhIL-22 or ESCs up-regulated CD105 expression on HUVECs and promoted angiogenesis, and α-IL-22 could reverse these effect induced by ESC. Compared to non-treated HUVECs, HUVECs educated by rh-IL-22 or ESCs could further up-regulate Ki-67 and proliferating cell nuclear antigen (PCNA) expression, and down-regulate Fas ligand (FasL) expression in ESCs. However, these effects induced by ESC-educated HUVECs were inhibited by α-IL-22. These results suggest that IL-22 derived from ESC promotes IL-22 receptors expression and enhances the viability, activation and angiogenesis of HUVEC. In turn, the educated HUVEC may further stimulate proliferation and restricts apoptosis of ESC. The integral effect may contribute to the progress of adenomyosis. Blocking IL-22 can disturb crosstalk between ESC and VEC mediated by IL-22, suggesting that blocking IL-22 may be a potential treatment strategy for adenomyosis.