INDUCTION OF INFLAMMATORY CYTOKINE RELEASE FROM CULTURED HUMAN MONOCYTES BY C-REACTIVE PROTEIN
INDUCTION OF INFLAMMATORY CYTOKINE RELEASE FROM CULTURED HUMAN MONOCYTES BY C-REACTIVE PROTEIN
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DOI：
10.1016/1043-4666(92)90079-7
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发表时间：
1992-09-01
期刊：
影响因子：
3.8
通讯作者：
LOZANSKI, G
中科院分区：
文献类型：
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作者：
BALLOU, SP;LOZANSKI, G
人急性时相蛋白C反应蛋白（CRP）能够特异性结合单核吞噬细胞并调节其功能。为了研究CRP是否也能影响这些细胞产生炎性细胞因子的能力，使用酶免疫测定和Western印迹技术定量新鲜分离的正常人单核细胞产生的白细胞介素1β（IL-1β）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）。CRP诱导每种细胞因子的快速释放，在培养4小时时培养上清液中的水平显著升高，TNF-α在培养8小时时达到最大水平，IL-1β和IL-6在培养16小时时达到最大水平。CRP的作用是剂量依赖性的;在用大于或等于50 μg/ml CRP培养后，观察到每种细胞因子增加超过10倍，该浓度通常在存在中度至重度炎症或组织损伤的情况下发现。CRP对细胞因子释放的诱导不受培养基中包含25 μg/ml多粘菌素-B的影响，但通过预先煮沸CRP完全消除，该程序对脂多糖诱导单核细胞细胞因子释放没有影响。CRP对炎性细胞因子的剂量依赖性诱导进一步支持了这一假设，即与单核吞噬细胞的相互作用构成了这种急性期蛋白的重要生物学作用。
The human acute phase protein, C-reactive protein (CRP), is capable of specifically binding to and modulating the function of mononuclear phagocytes. To investigate whether CRP can also affect the capacity of these cells to produce inflammatory cytokines, enzyme immunoassays and Western blot techniques were used to quantitate interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) produced by freshly-isolated normal human monocytes. CRP induced the rapid release of each cytokine, with significantly elevated levels in culture supernatants at 4 hours and maximal levels of TNF-α at 8 hours, and of IL-1β and IL-6 at 16 hours of culture. The effects of CRP were dose-dependent; greater than 10-fold increases of each cytokine were observed following culture with greater than or equal to 50 μg/ml CRP, concentrations which are often found in the presence of moderate to severe inflammation or tissue injury. The induction of cytokine release by CRP was unaffected by inclusion of 25 μg/ml polymyxin-B in culture media, but was completely abrogated by prior boiling of the CRP, a procedure which had no effect on induction of monocyte cytokine release by lipopolysaccaride. The dose-dependent induction of inflammatory cytokines by CRP provides further support for the hypothesis that interaction with mononuclear phagocytes constitutes an important biological role for this acute phase protein.