LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling
Yanping Hao1,2,3 | Liyan Wu1,2 | Yuhui Wang4 | Dongmei Shan1,2 | Yifei Liu1 | Jing Feng1,2 | Yi Chang3 | Ting Wang1,2,5,6
J Cell Mol Med 2024 Jul;28(13):e18509. doi: 10.1111/jcmm.18509.
- 1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
- 2University of Chinese Academy of Sciences, Beijing, China.
- 3Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
- 4Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 5Yunnan Key Laboratory of Gastrodia and Fungi Symbiotic Biology, Zhaotong University, Zhaotong, Yunnan, China.
- 6Yunnan Engineering Research Center of Green Planting and Processing of Gastrodia, Zhaotong University, Zhaotong, Yunnan, China.
PMID: 38957035 PMCID: PMC11220342 DOI: 10.1111/jcmm.18509
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.
Keywords: LPS; PI3K; TLR4; TRPV4; itch sensitization.
