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TLR4 enhances histamine-mediated pruritus by potentiating TRPV1 activity

Cited 30 time in Web of Science Cited 29 time in Scopus
Authors
Min, Hyunjung; Lee, Hyunkyoung; Lim, Hyoungsub; Jang, Yong Ho; Chung, Sung Jun; Lee, C Justin; Lee, Sung Joong
Issue Date
2014-08-21
Publisher
BioMed Central
Citation
Molecular Brain, 7(1):59
Keywords
Toll-like receptorItchSensory neurons
Abstract
Background
Recent studies have indicated that Toll-like receptor 4 (TLR4), a pathogen-recognition receptor that triggers inflammatory signals in innate immune cells, is also expressed on sensory neurons, implicating its putative role in sensory signal transmission. However, the possible function of sensory neuron TLR4 has not yet been formally addressed. In this regard, we investigated the role of TLR4 in itch signal transmission.

Results
TLR4 was expressed on a subpopulation of dorsal root ganglia (DRG) sensory neurons that express TRPV1. In TLR4-knockout mice, histamine-induced itch responses were compromised while TLR4 activation by LPS did not directly elicit an itch response. Histamine-induced intracellular calcium signals and inward currents were comparably reduced in TLR4-deficient sensory neurons. Reduced histamine sensitivity in the TLR4-deficient neurons was accompanied by a decrease in TRPV1 activity. Heterologous expression experiments in HEK293T cells indicated that TLR4 expression enhanced capsaicin-induced intracellular calcium signals and inward currents.

Conclusions
Our data show that TLR4 on sensory neurons enhances histamine-induced itch signal transduction by potentiating TRPV1 activity. The results suggest that TLR4 could be a novel target for the treatment of enhanced itch sensation.
Language
English
URI
http://hdl.handle.net/10371/109818
DOI
https://doi.org/10.1186/s13041-014-0059-9
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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