Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons

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. © 2017 the author(s).