title: 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.affiliation: Institute of Physiology 1, Jena University Hospital, Friedrich Schiller University Jena, Teichgraben 8, 07743 Jena, Germany. gban@mti.uni-jena.de
authors.forename: Gisela
authors.initials: G
authors.lastname: Segond von Banchet
authors.forename: Michael K
authors.initials: MK
authors.lastname: Boettger
authors.forename: Christian
authors.initials: C
authors.lastname: König
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020381:Interleukin-17; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C486576:Trpv4 protein, mouse