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

• Published in: Molecular and cellular neuroscience Vol. 52; pp. 152 - 160
• Main Authors: Segond von Banchet, Gisela, Boettger, Michael K., König, Christian, Iwakura, Yoichiro, Bräuer, Rolf, Schaible, Hans-Georg
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2013
• Subjects: Animals; Autoimmune diseases; Capsaicin receptors; Data processing; Dorsal root ganglia; ERK; Extracellular signal-regulated kinase; Ganglia, Spinal - metabolism; Hyperalgesia - metabolism; IL-17A; IL-17RA; Inflammation; Interleukin 1; Interleukin 17; Interleukin 6; Interleukin-17 - metabolism; Male; Mice; Mice, Knockout; Nervous system; Neurons; Neurons - metabolism; NFκB; Pain perception; Rats; Rats, Wistar; Rheumatoid arthritis; Signal Transduction - physiology; transient receptor potential proteins; TRPV Cation Channels - metabolism; TRPV1; TRPV4; Tumor necrosis factor- alpha; Up-Regulation; PBS; IL-17A; NFκB; Th17 cell; IL-17RA-like IR; TRPV1; COX; TNF-α; TRPV4; IL-17RA; 4αPDD; DRG; TTX; WT; ERK
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2012.11.006

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.