Possible pathophysiological roles of mitogen-activated protein kinases (MAPKs) in endometriosis
Possible pathophysiological roles of mitogen-activated protein kinases (MAPKs) in endometriosis
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DOI：
10.1111/j.1600-0897.2004.00231.x
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发表时间：
2004-11-01
影响因子：
3.6
通讯作者：
Taketani, Y
中科院分区：
文献类型：
--
作者：
Yoshino, O;Osuga, Y;Taketani, Y
问题：子宫内膜异位症伴有腹腔局部炎症反应。我们研究了磷酸化的丝裂原活化蛋白激酶（MAPK），即细胞外信号调节激酶（ERK），p38 MAPK（p38）和c-Jun N-末端激酶（JNK）在子宫内膜异位症的基质cells，和他们可能的病理生理作用，在子宫内膜异位症的关系，促炎物质。用Western blot法检测白细胞介素（IL）-1 β、肿瘤坏死因子（TNF）α和H2 O2处理的增生性基质细胞中MAPK磷酸化的情况。研究了ERK、p38和JNK抑制剂PD 98059、SB 202190和SP 600125对IL-1 β诱导的凋亡细胞分泌IL-6和IL-8以及IL-1 β诱导的环氧合酶-2（考克斯-2）表达的影响。结果：IL-1 β、TNF α和H2 O2可刺激ERK、p38和JNK的磷酸化，而各MAPK的蛋白总量与未刺激对照组相比无明显变化。SB 202190和SP 600125均抑制IL-1 β诱导的IL-6和IL-8分泌，PD 98059抑制IL-1 β诱导的IL-8分泌。SB 202190和PD 98059均抑制IL-1 β诱导的凋亡细胞中考克斯-2的表达。p38磷酸化率在子宫内膜异位症组织中显着高于那些在位的子宫内膜组织中的同一patients.CONCLUSIONS：鉴于目前的理论，炎症变化参与子宫内膜异位症的进展，MAPKs可以发挥关键的细胞内信号转导在子宫内膜异位症细胞，从而在疾病的病理生理作用。
PROBLEM: Endometriosis accompanies local inflammatory reactions in the peritoneal cavity. We examined the phosphorylation of mitogen-activated protein kinases (MAPKs), i.e. extracellular signal-regulated kinase (ERK), p38 MAPK (p38) and c-Jun N-terminal kinase (JNK) in endometriotic stromal cells, and their possible pathophysiological roles in endometriosis in relation to proinflammatory substances.METHOD OF STUDY: Endometriotic stromal cells were isolated from endometriomas and were cultured for the experiments. Phosphorylation of MAPKs in endometriotic stromal cells treated with interleukin (IL)-1beta, tumor necrosis factor (TNF)alpha and H2O2 were examined by Western blot analysis. Effects of PD98059, SB202190 and SP600125 (inhibitors of ERK, p38 and JNK, respectively) on IL-1beta-induced secretion of IL-6 and IL-8, and on IL-1beta-induced expression of cyclo-oxygenase-2 (COX-2) in endometriotic cells were studied. In addition, eutopic endometrial tissues were collected, and the phosphorylation rate of p38 in eutopic endometrial tissues and endometriotic tissues were determined.RESULTS: IL-1beta, TNFalpha and H2O2 stimulated the phosphorylation of ERK, p38 and JNK, while the total amounts of proteins of the respective MAPKs were virtually the same compared with those in the unstimulated controls. Both SB202190 and SP600125 suppressed IL-1beta-induced secretion of IL-6 and IL-8, and PD98059 suppressed IL-1beta-induced secretion of IL-8. Both SB202190 and PD98059 suppressed IL-1beta-induced expression of COX-2 in endometriotic cells. The p38 phosphorylation rates in the endometriotic tissues were significantly higher than those in the eutopic endometrial tissues of the same patients.CONCLUSIONS: Given the current theory that inflammatory changes are involved in the progression of endometriosis, MAPKs could play as pivotal intracellular signal transducers in endometriotic cells, and thus have a pathophysiological role in the disease.