PDF(Pubmed)
Abstract：
Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that lipopolysaccharides (LPS) could directly activate TRPV4 channel and TRPV4 is involved in the generation of both acute itch and chronic itch, whether and how LPS affects TRPV4-mediated itch sensation remains unclear. Here, we showed that LPS-mediated TRPV4 sensitization exacerbated GSK101-induced scratching behaviour in mice. Moreover, this effect was compromised in TLR4-knockout mice, suggesting LPS acted through a TLR4-dependent mechanism. Mechanistically, LPS enhanced GSK101-evoked calcium influx in mouse ear skin cells and HEK293T cells transfected with TRPV4. Further, LPS sensitized TRPV4 channel through the intracellular TLR4-PI3K-AKT signalling. In summary, our study found a modulatory role of LPS in TRPV4 function and highlighted the TLR4-TRPV4 interaction in itch signal amplification.
摘要：
瘙痒常伴有细菌感染，但是潜在的机制还没有完全理解。尽管先前的研究表明脂多糖（LPS）可以直接激活TRPV4通道，并且TRPV4参与了急性瘙痒和慢性瘙痒的产生。LPS是否以及如何影响TRPV4介导的瘙痒感觉尚不清楚.这里,我们发现LPS介导的TRPV4致敏作用加剧了GSK101诱导的小鼠抓挠行为.此外，这种效应在TLR4基因敲除小鼠中受损，提示LPS通过TLR4依赖性机制起作用。机械上,LPS增强小鼠耳皮肤细胞和TRPV4转染的HEK293T细胞中GSK101诱发的钙内流。Further,LPS通过细胞内TLR4-PI3K-AKT信号传导致敏TRPV4通道。总之,我们的研究发现了LPS在TRPV4功能中的调节作用,并强调了TLR4-TRPV4在瘙痒信号放大中的相互作用.
