Ostrowska Ewa, Reiser Georg
Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
Biochem Biophys Res Commun. 2008 Feb 22;366(4):1030-5. doi: 10.1016/j.bbrc.2007.12.064. Epub 2007 Dec 18.
The mechanism underlying protease-activated receptor (PAR)-activation and subsequent interleukin (IL)-8 production in airway epithelial cells is not yet understood. In this study we investigated the role of mitogen-activated protein kinases (MAPKs) in A549 airway epithelial cells. We studied the consequence of activation of PARs with simultaneous exposure to LPS. Thrombin, PAR-2-activating peptide and LPS, were tested alone and in combination. They induced significant synthesis of IL-8. However, only activation of PAR triggered phosphorylation of ERK1/2 and JNK. The application of the inhibitors of these two MAPKs resulted in reduction of IL-8 production. Thus, activation of PARs but not stimulation with LPS leads to ERK1/2 and JNK-mediated production of IL-8.
蛋白酶激活受体（PAR）激活及随后气道上皮细胞中白细胞介素（IL）-8产生的潜在机制尚不清楚。在本研究中，我们调查了丝裂原活化蛋白激酶（MAPK）在A549气道上皮细胞中的作用。我们研究了PARs激活同时暴露于脂多糖（LPS）的后果。单独及联合测试了凝血酶、PAR-2激活肽和LPS。它们诱导了IL-8的显著合成。然而，只有PAR的激活触发了细胞外信号调节激酶1/2（ERK1/2）和应激活化蛋白激酶（JNK）的磷酸化。这两种MAPK抑制剂的应用导致IL-8产生减少。因此，PARs的激活而非LPS刺激导致ERK1/2和JNK介导的IL-8产生。
