Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells:: Synergy with interleukin-1β and tumor necrosis factor-α
Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells:: Synergy with interleukin-1β and tumor necrosis factor-α
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DOI：
10.1016/s0022-5347(05)00167-9
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发表时间：
2006-02-01
影响因子：
6.6
通讯作者：
Bouchelouche, P
中科院分区：
文献类型：
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作者：
Bouchelouche, K;Andresen, L;Bouchelouche, P
目的：间质性膀胱炎的特征是逼尿肌中激活的MC数量增加。然而，据我们所知，影响MC和HDSMC之间解剖关系的因素尚不清楚。MCP-1、IL-6和SCF在MC发育、信号传导和功能的调节中具有关键作用。我们研究了HDSMCs是否能够表达和释放MCP-1，IL-6和SCF响应IL-4，IL-13，IL-1 β和肿瘤坏死因子-a.Materials和方法：HDSMCs分离和培养使用外植体技术。半定量逆转录-聚合酶链反应（RT-PCR）和特异性酶联免疫吸附试验（ELISA）检测细胞蛋白表达及MCP-1、IL-6和SCF的分泌。在IL-4刺激的细胞中，MCP-1 mRNA上调的平均因子+/- SD为3.5 +/- 1.3，IL-6 mRNA上调的平均因子为3.8 +/- 1.3，可溶性SCF上调的平均因子为3.2 +/- 0.6，膜结合型SCF上调的平均因子为7.9 +/- 5.6。对于IL-13刺激的细胞，值分别为2.6 +/- 1.5、3.6 +/- 2.1、2.9 +/- 1.6和5.7 +/- 3.7。可溶性SCF mRNA的表达是mSCF mRNA表达的5倍。分别给予IL-4和IL-13以浓度（0.01 - 100 ng/ml）和时间（0 - 24小时）依赖的方式刺激MCP-1、IL-6和SCF的分泌。此外，IL-1 β和肿瘤坏死因子-α单独诱导MCP-1，IL-6和SCF的显着释放，但在与IL-4或IL-13的组合，它诱导更大的分泌MCP-1，IL-6和SCF.Conclusions：据我们所知，这些研究结果首次证明，HDSMCs表达和释放MCP-1和IL-6，并表现出相对较高的可溶性SCF的表达。这支持了我们的假设，即HDSMCs可能通过协调膀胱壁中的局部炎症反应而发挥积极作用，并可能影响逼尿肌肥大细胞增多症的病理生理学。
Purpose: Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development, signaling and function. We investigated whether HDSMCs are capable of expressing and releasing MCP-1, IL-6 and SCF in response to IL-4, IL-13, IL-1 beta and tumor necrosis factor-a.Materials and Methods: HDSMCs were isolated and cultured using an explant technique. Protein expression, and the secretion of MCP-1, IL-6 and SCF were assayed by semiquantitative reverse transcriptase-polymerase chain reaction and specific enzyme-linked immunosorbent assay.Results: Unstimulated cells released low amounts of MCP-1, IL-6 and SCF. In cells stimulated by IL-4 MCP-1 mRNA was up-regulated by a mean factor +/- SD of 3.5 +/- 1.3, IL-6 mRNA was up-regulated by 3.8 +/- 1.3, the soluble form of SCF was up-regulated by 3.2 +/- 0.6 and the membrane bound form of SCF was up-regulated by 7.9 +/- 5.6. For IL-13 stimulated cells the values were 2.6 +/- 1.5, 3.6 +/- 2.1, 2.9 +/- 1.6 and 5.7 +/- 3.7, respectively. Soluble SCF mRNA expression was 5 times higher than the expression of mSCF mRNA. IL-4 and IL-13 given separately stimulated MCP-1, IL-6 and SCF secretion in a concentration (0.01 to 100 ng/ml) and time (0 to 24 hours) dependent manner. Furthermore, IL-1 beta and tumor necrosis factor-a alone induced significant release of MCP-1, IL-6 and SCF but in combination with IL-4 or IL-13 it induced greater secretion of MCP-1, IL-6 and SCF.Conclusions: To our knowledge these findings demonstrate for the first time that HDSMCs express and release MCP-1 and IL-6, and show relatively high expression of soluble SCF. This supports our hypothesis that HDSMCs may have an active role by orchestrating the local inflammatory response in the bladder wall with possible implications for the pathophysiology of detrusor mastocytosis.