Journal article

Publication year: 2005

Pages: 1634-1641

Journal: Brain

Volume number: 128

ISSN: 0006-8950

eISSN: 1460-2156

DOI Link: https://doi.org/10.1093/brain/awh490

Publisher: Oxford University Press

Abstract: 
The pro-inflammatory cytokine interleukin-6 (IL-6) together with its soluble receptor (sIL-6R) induces and maintains thermal hyperalgesia. It facilitates the heat-induced release of calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Here we report that exposure of nociceptive neurons to the IL-6-sIL-6R complex or the gp130-stimulating designer IL-6-sIL-6R fusion protein Hyper-IL-6 (HIL-6) resulted in a potentiation of heat-activated inward currents (I-heat) and a shift of activation thresholds towards lower temperatures without affecting intracellular calcium levels. The Janus tyrosine kinase inhibitor AG490, the selective protein kinase C (PKC) inhibitor, bisindolylmaleimide 1 (BIM1), as well as rottlerin, a selective blocker of the PKC delta isoform, but not the cyclooxygenase inhibitor indomethacin, effectively reduced the effect. Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization revealed expression of mRNA for the signal-transducing beta subunit of the receptor gp130 in neuronal somata, rather than satellite cells in rat dorsal root ganglia. Together, the results suggest that IL-6-sIL-6R acts directly on sensory neurons. It increases their susceptibility to noxious heat via the gp130/Jak/PKC delta signalling pathway.

Harvard Citation style: Obreja, O., Biasio, W., Andratsch, M., Lips, K., Rathee, P., Ludwig, A., et al. (2005) Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons, Brain, 128, pp. 1634-1641. https://doi.org/10.1093/brain/awh490

APA Citation style: Obreja, O., Biasio, W., Andratsch, M., Lips, K., Rathee, P., Ludwig, A., Rose-John, S., & Kress, M. (2005). Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons. Brain. 128, 1634-1641. https://doi.org/10.1093/brain/awh490