Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons
| العنوان: | Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons |
|---|---|
| المؤلفون: | Min-Hee Yi, Yonghyun Kim, Hyo Jung Shin, Hyunjung Baek, Cuk-Seong Kim, Enji Zhang, J.W. Kim, Jinpyo Hong, Joon Won Kang, Sena Kim, Dong Woon Kim, Nara Shin |
| المصدر: | Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-10 (2017) Journal of Neuroinflammation |
| بيانات النشر: | BMC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cell signaling, Lipopolysaccharide, medicine.medical_treatment, Immunology, Biology, Hippocampal formation, Hippocampus, lcsh:RC346-429, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, Primary cilia, Neuroinflammation, medicine, Animals, KIF3A, Cilia, TLR4, lcsh:Neurology. Diseases of the nervous system, NFκb, Inflammation, Mice, Knockout, Neurons, General Neuroscience, Cilium, Research, NF-kappa B, Cell biology, Mice, Inbred C57BL, Toll-Like Receptor 4, 030104 developmental biology, Cytokine, Neurology, chemistry, Neuroscience, Signal Transduction |
| الوصف: | Background The primary cilium is an organelle that can act as a master regulator of cellular signaling. Despite the presence of primary cilia in hippocampal neurons, their function is not fully understood. Recent studies have demonstrated that the primary cilium influences interleukin (IL)-1β-induced NF-κB signaling, ultimately mediating the inflammatory response. We, therefore, investigated ciliary function and NF-κB signaling in lipopolysaccharide (LPS)-induced neuroinflammation in conjunction with ciliary length analysis. Methods Since TLR4/NF-κB signaling is a well-known inflammatory pathway, we measured ciliary length and inflammatory mediators in wild type (WT) and TLR4−/− mice injected with LPS. Next, to exclude the effects of microglial TLR4, we examined the ciliary length, ciliary components, inflammatory cytokine, and mediators in HT22 hippocampal neuronal cells. Results Primary ciliary length decreased in hippocampal pyramidal neurons after intracerebroventricular injection of LPS in WT mice, whereas it increased in TLR4−/− mice. LPS treatment decreased primary ciliary length, activated NF-κB signaling, and increased Cox2 and iNOS levels in HT22 hippocampal neurons. In contrast, silencing Kif3a, a key protein component of cilia, increased ARL13B ciliary protein levels and suppressed NF-κB signaling and expression of inflammatory mediators. Conclusions These data suggest that LPS-induced NF-κB signaling and inflammatory mediator expression are modulated by cilia and that the blockade of primary cilium formation by Kif3a siRNA regulates TLR4-induced NF-κB signaling. We propose that primary cilia are critical for regulating NF-κB signaling events in neuroinflammation and in the innate immune response. Electronic supplementary material The online version of this article (10.1186/s12974-017-0958-7) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1742-2094 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f95c103f78e5b4f49e487655269ceac1Test http://link.springer.com/article/10.1186/s12974-017-0958-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f95c103f78e5b4f49e487655269ceac1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17422094 |
|---|