Obreja Otilia, Rathee Parvinder K, Lips Kathrin S, Distler Carsten, Kress Michaela
Institut fuer Physiologie und Experimentelle Pathophysiologie, Friedrich-Alexander Universitaet, 91054 Erlangen, Germany.
FASEB J. 2002 Oct;16(12):1497-503. doi: 10.1096/fj.02-0101com.
Interleukin 1 beta (IL-1 beta) is a proinflammatory cytokine that maintains thermal hyperalgesia and facilitates the release of calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Brief applications of IL-1 beta to nociceptive neurons yielded a potentiation of heat-activated inward currents (Iheat) and a shift of activation threshold toward lower temperature without altering intracellular calcium levels. The IL-1 beta-induced heat sensitization was not dependent on G-protein-coupled receptors but was mediated by activation of protein kinases. The nonspecific protein kinase inhibitor staurosporine, the specific protein kinase C inhibitor bisindolylmaleimide BIM1, and the protein tyrosine kinase inhibitor genistein reduced the sensitizing effect of IL-1 beta whereas negative controls were ineffective. RT-PCR and in situ hybridization revealed IL-1RI but not RII expression in neurons rather than surrounding satellite cells in rat dorsal root ganglia. IL-1 beta acts on sensory neurons to increase their susceptibility for noxious heat via an IL-1RI/PTK/PKC-dependent mechanism.
白细胞介素1β（IL-1β）是一种促炎细胞因子，在体内和体外均可维持热痛觉过敏，并促进大鼠皮肤伤害感受器释放降钙素基因相关肽。将IL-1β短暂应用于伤害性神经元可增强热激活内向电流（Iheat），并使激活阈值向低温方向移动，而不改变细胞内钙水平。IL-1β诱导的热敏化不依赖于G蛋白偶联受体，而是由蛋白激酶的激活介导的。非特异性蛋白激酶抑制剂星形孢菌素、特异性蛋白激酶C抑制剂双吲哚马来酰胺BIM1和蛋白酪氨酸激酶抑制剂染料木黄酮可降低IL-1β的敏化作用，而阴性对照则无效。逆转录聚合酶链反应（RT-PCR）和原位杂交显示，在大鼠背根神经节中，神经元而非周围卫星细胞表达IL-1RI而非RII。IL-1β通过IL-1RI/PTK/PKC依赖性机制作用于感觉神经元，增加其对伤害性热的敏感性。
