Jabłońska Ewa, Wawrusiewicz-Kurylonek Natalia, Garley Marzena, Krętowski Adam
Department of Immunology, Medical University of Bialystok, Poland.
Folia Histochem Cytobiol. 2012 Jul 5;50(2):196-202. doi: 10.5603/fhc.2012.0029.
In the present study we investigate the consequences of TLR4 activation by LPS for the synthesis of a proliferation-inducing ligand (APRIL) by human neutrophils (PMNs), and the possible role of the ERK1/2 kinases signaling pathway. In order to make a comparison, the same examinations were carried out on autologous peripheral blood mononuclear cells (PBMCs). The levels of mRNA for APRIL and TLR4 were measured using the real-time PCR method. Western blot analysis was used to assay the expressions of APRIL and ERK1/2 in cell lysates. We discovered an increased expression of APRIL accompanying the increased expression of TLR4 in the LPS-stimulated PMNs and PBMCs. Furthermore, stimulation with LPS triggered similar changes in phospho-ERK1/2 proteins expression in those cells. The present study suggests that LPS plays a role in TLR4-ligation in APRIL induction through ERK1/2 pathway activation in human neutrophils and mononuclear cells of peripheral blood. The association between TLR4 activation and APRIL expression in examined leukocytes might have important implications for the immune response of the host exposed to TLR4 ligands such as LPS.
在本研究中,我们探究了脂多糖(LPS)激活Toll样受体4(TLR4)对人中性粒细胞(PMN)合成增殖诱导配体(APRIL)的影响,以及细胞外信号调节激酶1/2(ERK1/2)信号通路可能发挥的作用。为作比较,我们对自体外周血单个核细胞(PBMC)进行了同样的检测。采用实时聚合酶链反应(PCR)法测定APRIL和TLR4的信使核糖核酸(mRNA)水平。蛋白质免疫印迹分析用于检测细胞裂解液中APRIL和ERK1/2的表达。我们发现,在LPS刺激的PMN和PBMC中,随着TLR4表达增加,APRIL的表达也增加。此外,LPS刺激引发了这些细胞中磷酸化ERK1/2蛋白表达的类似变化。本研究表明,LPS通过激活人中性粒细胞和外周血单个核细胞中的ERK1/2通路,在TLR4连接介导的APRIL诱导过程中发挥作用。在受检白细胞中,TLR4激活与APRIL表达之间的关联可能对暴露于LPS等TLR4配体的宿主免疫反应具有重要意义。