Kohoutková Marcela, Korimová Andrea, Brázda Václav, Kohoutek Jiří, Dubový Petr
Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Kamenice 3, 625 00, Brno, Czech Republic.
Faculty of Science, RECETOX-Research Centre for Toxic Compounds in the Environment, Masaryk University, Brno, Czech Republic.
Histochem Cell Biol. 2017 Dec;148(6):607-615. doi: 10.1007/s00418-017-1601-5. Epub 2017 Jul 28.
Inflammatory profiling of Schwann cells manifested as an upregulation of cytokines is present after traumatic or disease injury of the peripheral nerves. Inflammatory activation of Schwann cells via Toll-like receptors (TLRs) can be triggered by exogenous pathological molecules or endogenous ligands produced during Wallerian degeneration. We investigated the early period of inflammatory reactions by following the levels of TLR4, NFκB, IL-1β, pSTAT3, and IL-6 proteins after LPS treatment of RT4 schwannoma cells under in vitro conditions. Significantly increased levels of NFκB, IL-1β, pSTAT3, and IL-6 proteins were found 1 h after LPS action indicating their involvement in the initiation of the inflammatory reaction of schwannoma cells. This initiation was induced without increased TLR4 protein expression, but was accompanied by the appearance of TLR4 in early endosomes. The protein levels decreased within the next 6 h of treatment with a subsequent increase of NFκB, IL-1β, and pSTAT3 after 24 h of LPS treatment. In contrast, continuous decrease of IL-6 over time following LPS treatment was unexpected. Levels of soluble IL-6 protein in the culture medium also decreased with decreasing levels of LPS over 24 h.
雪旺细胞的炎症特征表现为细胞因子上调,在外周神经受到创伤或疾病损伤后出现。通过Toll样受体(TLR)对雪旺细胞的炎症激活可由外源性病理分子或沃勒变性过程中产生的内源性配体触发。我们在体外条件下用脂多糖(LPS)处理RT4雪旺瘤细胞后,通过追踪TLR4、NFκB、IL-1β、pSTAT3和IL-6蛋白的水平来研究炎症反应的早期阶段。在LPS作用1小时后,发现NFκB、IL-1β、pSTAT3和IL-6蛋白水平显著升高,表明它们参与了雪旺瘤细胞炎症反应的起始。这种起始在TLR4蛋白表达未增加的情况下被诱导,但伴随着早期内体中TLR4的出现。在接下来的6小时处理过程中,蛋白水平下降,在LPS处理24小时后,NFκB、IL-1β和pSTAT3随后增加。相比之下,LPS处理后IL-6随时间持续下降是出乎意料的。在24小时内,随着LPS水平的降低,培养基中可溶性IL-6蛋白水平也下降。