Neuronal IL-17 receptor upregulates TRPV4 but not TRPV1 receptors in DRG neurons and mediates mechanical but not thermal hyperalgesia.

Abstract

In addition to the proinflammatory cytokines tumor necrosis factor-α, interleukin-6 and interleukin-1ß, the cytokine interleukin-17 (IL-17) is considered an important mediator of autoimmune diseases such as rheumatoid arthritis. Because tumor necrosis factor-α and interleukin-1ß have the potential to influence the expression of transduction molecules such as transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglion (DRG) neurons and thus to contribute to pain we explored in the present study whether IL-17A activates DRG neurons and influences the expression of TRPV1. The IL-17A receptor was visualized in most neurons in dorsal root ganglion (DRG) sections as well as in cultured DRG neurons. Upon long-term exposure to IL-17A, isolated and cultured rat DRG neurons showed a significant upregulation of extracellular-regulated kinase (ERK) and nuclear factor κB (NFκB). Long-term exposure of neurons to IL-17A did not upregulate the expression of TRPV1. However, we found a pronounced upregulation of transient receptor potential vanilloid 4 (TRPV4) which is considered a candidate transduction molecule for mechanical hyperalgesia. Upon the injection of zymosan into the paw, IL-17A-deficient mice showed less mechanical hyperalgesia than wild type mice but thermal hyperalgesia was not attenuated in IL-17A-deficient mice. These data show, therefore, a particular role of IL-17 in mechanical hyperalgesia, and they suggest that this effect is linked to an activation and upregulation of TRPV4.

• Authors: Gisela Segond von Banchet, Michael K Boettger, Christian König, Yoichiro Iwakura, Rolf Bräuer, Hans-Georg Schaible
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 52 Pg. 152-60 (Jan 2013) ISSN: 1095-9327 [Electronic] United States
• PMID: 23147107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-17
• TRPV Cation Channels
• TRPV1 protein, mouse
• Trpv4 protein, mouse

Topics

• Animals
• Ganglia, Spinal (metabolism)
• Hyperalgesia (metabolism)
• Interleukin-17 (metabolism)
• Male
• Mice
• Mice, Knockout
• Neurons (metabolism)
• Rats
• Rats, Wistar
• Signal Transduction (physiology)
• TRPV Cation Channels (metabolism)
• Up-Regulation