Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue.
Calcium sensing receptor activation elevates proinflammatory factor expression in human adipose cells and adipose tissue.
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DOI：
10.1016/j.mce.2012.03.006
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发表时间：
2012-09-25
影响因子：
4.1
通讯作者：
Reyes, Marcela
中科院分区：
文献类型：
--
作者：
Cifuentes, Mariana;Fuentes, Cecilia;Tobar, Nicolas;Acevedo, Ingrid;Villalobos, Elisa;Hugo, Eric;Ben-Jonathan, Nira;Reyes, Marcela
我们先前已经确定，人脂肪细胞和人脂肪细胞系LS 14表达钙敏感受体（CaSR），并且其表达在暴露于肥胖人中通常升高的炎性细胞因子后升高。近年来的研究已经确定，肥胖的不良代谢和心血管后果的重要部分源自组织功能障碍，其中一种机制是导致促炎细胞因子和趋化因子过量的紊乱分泌模式。考虑到已报道的CaSR与其他组织炎症过程的相关性，我们试图评估其在提高炎症因子脂肪表达中的作用。我们将脂肪组织和体外培养的LS 14前脂肪细胞和分化的脂肪细胞暴露于拟钙西那卡塞，并评估促炎细胞因子IL 6、IL 1 β和TNFα以及趋化因子CCL 2的表达或产生。CaSR激活引起炎症因子表达升高，这部分被炎症介质NFκB的抑制剂SN 50逆转。我们的观察结果表明，CaSR激活通过涉及NFκB核转位激活的信号通路提高细胞因子和趋化因子的产生。这些发现证实了CaSR在肥胖诱导的脂肪组织功能障碍的病理生理学中的相关性，具有在对抗肥胖相关疾病中进行药理学操作的有趣潜力。
We have previously established that human adipose cells and the human adipose cell line LS14 express the calcium sensing receptor (CaSR) and that its expression is elevated upon exposure to inflammatory cytokines that are typically elevated in obese humans. Research in recent years has established that an important part of the adverse metabolic and cardiovascular consequences of obesity derive from a dysfunction of the tissue, one of the mechanisms being a disordered secretion pattern leading to an excess of proinflammatory cytokines and chemokines. Given the reported association of the CaSR to inflammatory processes in other tissues, we sought to evaluate its role elevating the adipose expression of inflammatory factors. We exposed adipose tissue and in-vitro cultured LS14 preadipocytes and differentiated adipocytes to the calcimimetic cinacalcet and evaluated the expression or production of the proinflammatory cytokines IL6, IL1β and TNFα as well as the chemoattractant factor CCL2. CaSR activation elicited an elevation in the expression of the inflammatory factors, which was in part reverted by SN50, an inhibitor of the inflammatory mediator NFκB. Our observations suggest that CaSR activation elevates cytokine and chemokine production through a signaling pathway involving activation of NFκB nuclear translocation. These findings confirm the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction, with an interesting potential for pharmacological manipulation in the fight against obesity- associated diseases.
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