Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells
Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells
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DOI：
10.1093/humrep/dei255
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发表时间：
2005-12-01
影响因子：
6.1
通讯作者：
Taketani, Y
中科院分区：
文献类型：
--
作者：
Hirota, Y;Osuga, Y;Taketani, Y
背景技术背景：炎症被认为在子宫内膜异位症的病理生理学中起重要作用，其中嗜中性粒细胞和肥大细胞被认为参与其中。我们研究了蛋白酶激活受体2（PAR 2），这是激活的中性粒细胞和肥大细胞的酶，在增生性基质细胞（ESC）是否有任何意义的发展，疾病。方法：用不同浓度的特异性PAR 2激动剂肽刺激培养的ESC。使用增殖细胞核抗原（细胞增殖标记物）的免疫染色、5-溴-2 '-脱氧尿苷掺入DNA和细胞计数来测定细胞的增殖活性。采用特异性酶联免疫吸附测定试剂盒测定白细胞介素（IL）-6和IL-8的浓度。用Western blot方法检测p38 MAPK、p42/44 MAPK和应激活化蛋白激酶/c-jun N末端激酶（stress-activated protein Kinase/c-jun N terminal Kinase，MAPK）在ESC中的磷酸化水平。结果：PAR 2激活可促进ESC增殖，并呈剂量依赖性地刺激ESC分泌IL-6和IL-8。PAR 2的激活刺激了所有三种MAPK的磷酸化，并且每种MAPK的抑制剂抑制PAR 2激活诱导的ESC增殖。结论：ESC中PAR 2的激活可能通过诱导子宫内膜异位症病变的生长和炎症而参与子宫内膜异位症的病理生理过程。
BACKGROUND: Inflammation has been proposed to play essential roles in the pathophysiology of endometriosis, in which neutrophils and mast cells have been suggested to be involved. We studied whether the protease-activated receptor 2 (PAR2), which is activated by enzymes from neutrophils and mast cells, in endometriotic stromal cells (ESC) has any implication in the development of the disease. METHODS: Cultured ESC were stimulated with various concentrations of a specific PAR2 agonist peptide. Proliferating activity of the cells was determined using immunostaining of proliferating cell nuclear antigen (a cell proliferation marker), 5-bromo-2'-deoxyuridine incorporation into DNA and cell count. The concentrations of interleukin (IL)-6 and IL-8 were measured using specific enzyme-linked immunosorbent assay kits. The phosphorylation of three mitogen-activated protein kinases (MAPK), i.e. p38 MAPK, p42/44 MAPK and stress-activated protein Kinase/c-jun N terminal Kinase, in ESC was examined with Western blot analysis. RESULTS: Activation of PAR2 stimulated the proliferation of ESC and the secretion of IL-6 and IL-8 from ESC in a dose-dependent manner. Activation of PAR2 stimulated the phosphorylation of all three MAPK, and inhibitors of each MAPK suppressed the PAR2 activation-induced proliferation of ESC. CONCLUSIONS: The activation of PAR2 in ESC may be involved in the pathophysiology of endometriosis by inducing the growth and inflammation of endometriotic lesions.