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Differential effects of lipopolysaccharide on mouse sensory TRP channels.
Cell Calcium. 2018 07; 73:72-81.CC

Abstract

Acute neurogenic inflammation and pain associated to bacterial infection have been traditionally ascribed to sensitization and activation of sensory nerve afferents secondary to immune cell stimulation. However, we recently showed that lipopolysaccharides (LPS) directly activate the Transient Receptor Potential channels TRPA1 in sensory neurons and TRPV4 in airway epithelial cells. Here we investigated whether LPS activates other sensory TRP channels expressed in sensory neurons. Using intracellular Ca2+ imaging and patch-clamp we determined the effects of LPS on recombinant TRPV1, TRPV2, TRPM3 and TRPM8, heterologously expressed in HEK293T cells. We found that LPS activates TRPV1, although with lower potency than for TRPA1. Activation of TRPV1 by LPS was not affected by mutations of residues required for activation by electrophilic agents or by diacylglycerol and capsaicin. On the other hand, LPS weakly activated TRPM3, activated TRPM8 at 25 °C, but not at 35 °C, and was ineffective on TRPV2. Experiments performed in mouse dorsal root ganglion (DRG) neurons revealed that genetic ablation of Trpa1 did not abolish the responses to LPS, but remain detected in 30% of capsaicin-sensitive cells. The population of neurons responding to LPS was dramatically lower in double Trpa1/Trpv1 KO neurons. Our results show that, in addition to TRPA1, other TRP channels in sensory neurons can be targets of LPS, suggesting that they may contribute to trigger and regulate innate defenses against gram-negative bacterial infections.

Authors+Show Affiliations

Laboratory for Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, O&N1 Herestraat 49 - box 802, 3000, Leuven, Belgium.Laboratory for Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, O&N1 Herestraat 49 - box 802, 3000, Leuven, Belgium.Laboratory for Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, O&N1 Herestraat 49 - box 802, 3000, Leuven, Belgium.Laboratory for Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, O&N1 Herestraat 49 - box 802, 3000, Leuven, Belgium.Laboratory for Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, O&N1 Herestraat 49 - box 802, 3000, Leuven, Belgium.Laboratory for Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, O&N1 Herestraat 49 - box 802, 3000, Leuven, Belgium. Electronic address: karel.talavera@kuleuven.vib.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29689522

Citation

Boonen, Brett, et al. "Differential Effects of Lipopolysaccharide On Mouse Sensory TRP Channels." Cell Calcium, vol. 73, 2018, pp. 72-81.
Boonen B, Alpizar YA, Sanchez A, et al. Differential effects of lipopolysaccharide on mouse sensory TRP channels. Cell Calcium. 2018;73:72-81.
Boonen, B., Alpizar, Y. A., Sanchez, A., López-Requena, A., Voets, T., & Talavera, K. (2018). Differential effects of lipopolysaccharide on mouse sensory TRP channels. Cell Calcium, 73, 72-81. https://doi.org/10.1016/j.ceca.2018.04.004
Boonen B, et al. Differential Effects of Lipopolysaccharide On Mouse Sensory TRP Channels. Cell Calcium. 2018;73:72-81. PubMed PMID: 29689522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of lipopolysaccharide on mouse sensory TRP channels. AU - Boonen,Brett, AU - Alpizar,Yeranddy A, AU - Sanchez,Alicia, AU - López-Requena,Alejandro, AU - Voets,Thomas, AU - Talavera,Karel, Y1 - 2018/04/14/ PY - 2018/01/08/received PY - 2018/03/24/revised PY - 2018/04/10/accepted PY - 2018/4/25/pubmed PY - 2019/5/10/medline PY - 2018/4/25/entrez KW - Endotoxin KW - LPS KW - Sensory neuron KW - TRPA1 KW - TRPM3 KW - TRPM8 KW - TRPV1 SP - 72 EP - 81 JF - Cell calcium JO - Cell Calcium VL - 73 N2 - Acute neurogenic inflammation and pain associated to bacterial infection have been traditionally ascribed to sensitization and activation of sensory nerve afferents secondary to immune cell stimulation. However, we recently showed that lipopolysaccharides (LPS) directly activate the Transient Receptor Potential channels TRPA1 in sensory neurons and TRPV4 in airway epithelial cells. Here we investigated whether LPS activates other sensory TRP channels expressed in sensory neurons. Using intracellular Ca2+ imaging and patch-clamp we determined the effects of LPS on recombinant TRPV1, TRPV2, TRPM3 and TRPM8, heterologously expressed in HEK293T cells. We found that LPS activates TRPV1, although with lower potency than for TRPA1. Activation of TRPV1 by LPS was not affected by mutations of residues required for activation by electrophilic agents or by diacylglycerol and capsaicin. On the other hand, LPS weakly activated TRPM3, activated TRPM8 at 25 °C, but not at 35 °C, and was ineffective on TRPV2. Experiments performed in mouse dorsal root ganglion (DRG) neurons revealed that genetic ablation of Trpa1 did not abolish the responses to LPS, but remain detected in 30% of capsaicin-sensitive cells. The population of neurons responding to LPS was dramatically lower in double Trpa1/Trpv1 KO neurons. Our results show that, in addition to TRPA1, other TRP channels in sensory neurons can be targets of LPS, suggesting that they may contribute to trigger and regulate innate defenses against gram-negative bacterial infections. SN - 1532-1991 UR - https://www.unboundmedicine.com/medline/citation/29689522/Differential_effects_of_lipopolysaccharide_on_mouse_sensory_TRP_channels_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4160(18)30002-2 DB - PRIME DP - Unbound Medicine ER -