Browsing by Author "Hong, Jinpyo"

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    Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons
    (Biomed Central, 2017) Baek, Hyunjung; Shin, Hyo Jung; Kim, Jwa-Jin; Shin, Nara; Kim, Sena; Yi, Min-Hee; Zhang, Enji; Hong, Jinpyo; Kang, Joon Won; Kim, Yonghyun; Kim, Cuk-Seong; Kim, Dong Woon; Chungnam National University; Chungnam National University Hospital; University of Texas Medical Branch Galveston; Yanbian University; University of Alabama Tuscaloosa
    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)-1 beta-induced NF-kappa B signaling, ultimately mediating the inflammatory response. We, therefore, investigated ciliary function and NF-kappa B signaling in lipopolysaccharide (LPS)-induced neuroinflammation in conjunction with ciliary length analysis. Methods: Since TLR4/NF-kappa B 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-kappa B 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-kappa B signaling and expression of inflammatory mediators. Conclusions: These data suggest that LPS-induced NF-kappa B signaling and inflammatory mediator expression are modulated by cilia and that the blockade of primary cilium formation by Kif3a siRNA regulates TLR4-induced NF-kappa B signaling. We propose that primary cilia are critical for regulating NF-kappa B signaling events in neuroinflammation and in the innate immune response.
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    TLR4-mediated autophagic impairment contributes to neuropathic pain in chronic constriction injury mice
    (Biomed Central, 2018) Piao, Yibo; Gwon, Do Hyeong; Kang, Dong-Wook; Hwang, Tae Woong; Shin, Nara; Kwon, Hyeok Hee; Shin, Hyo Jung; Yin, Yuhua; Kim, Jwa-Jin; Hong, Jinpyo; Kim, Hyun-Woo; Kim, Yonghyun; Kim, Sang Ryong; Oh, Sang-Ha; Kim, Dong Woon; Chungnam National University; Chungnam National University Hospital; University of Alabama Tuscaloosa; Kyungpook National University
    Neuropathic pain is a complex, chronic pain state characterized by hyperalgesia, allodynia, and spontaneous pain. Accumulating evidence has indicated that the microglial Toll-like receptor 4 (TLR4) and autophagy are implicated in neurodegenerative diseases, but their relationship and role in neuropathic pain remain unclear. In this study, we examined TLR4 and its association with autophagic activity using a chronic constriction injury (CCI)-induced neuropathic pain model in wild-type (WT) and TLR4-knockout (KO) mice. The mice were assigned into four groups: WT-Contralateral (Contra), WT-Ipsilateral (Ipsi), TLR4 KO-Contra, and TLR4 KO-Ipsi. Behavioral and mechanical allodynia tests and biochemical analysis of spinal cord tissue were conducted following CCI to the sciatic nerve. Compared with the Contra group, mechanical allodynia in both the WT-and TLR4 KO-Ipsi groups was significantly increased, and a marked decrease of allodynia was observed in the TLR4 KO-Ipsi group. Although glial cells were upregulated in the WT-Ipsi group, no significant change was observed in the TLR4 KO groups. Moreover, protein expression and immunoreactive cell regulation of autophagy (Beclin 1, p62) were significantly increased in the neurons, but not microglia, of WT-Ipsi group compared with the WT-Contra group. The level of PINK1, a marker for mitophagy was increased in the neurons of WT, but not in TLR4 KO mice. Together, these results show that TLR4-mediated p62 autophagic impairment plays an important role in the occurrence and development of neuropathic pain. And what is more, microglial TLR4-mediated microglial activation might be indirectly coupled to neuronal autophage.