Abstract:
The primary cilium is a characteristic feature of most non-immune cells and functions as an environmental signal transduction sensor. The defects in primary cilium have profound effects on the developmental program, including the maturation of retinal epithelium. The ciliary length is tightly regulated during ciliogenesis, but the impact of inflammation on ciliary length remains elusive. The current study investigates the outcome of inflammatory stimuli for the primary cilium length in retinal epithelium cells and mouse embryonic fibroblasts. Here, we report that exposure to the pro-inflammatory cytokine TNF-alpha elongates cilia in a mixed-lineage kinase (MLK)-dependent manner. Pro-inflammatory stimuli such as bacterial LPS and interferon-gamma have similar effects on ciliary length. In contrast, febrile condition-mimicking heat stress dramatically reduced the number of ciliated cells regardless of TNF-alpha exposure but did not shorten TNF-induced elongation, suggesting distinct but rapid effects of inflammatory stresses on ciliogenesis.
摘要:
初级纤毛是大多数非免疫细胞的特征,并充当环境信号转导传感器。原发性纤毛的缺陷对发育程序有深远的影响,包括视网膜上皮的成熟.纤毛长度在纤毛发生过程中受到严格调节,但是炎症对纤毛长度的影响仍然难以捉摸。目前的研究调查了炎症刺激对视网膜上皮细胞和小鼠胚胎成纤维细胞中原代纤毛长度的影响。这里,我们报道,暴露于促炎细胞因子TNF-α会以混合谱系激酶(MLK)依赖性方式延长纤毛.促炎性刺激如细菌LPS和干扰素-γ对纤毛长度具有类似的作用。相比之下,高热条件模拟热应激显著减少纤毛细胞的数量,而不管TNF-α暴露,但没有缩短TNF诱导的伸长,提示炎症应激对纤毛生成的明显但快速的影响。