2024-03-28T20:02:20Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/856422022-11-17T02:08:08Zhdl_2115_20048hdl_2115_140Alpha and beta adrenoceptors activate interleukin-6 transcription through different pathways in cultured astrocytes from rat spinal cordMorimoto, Kohei1000010846067Eguchi, RyotaKitano, Taisuke1000040344494Otsuguro, Ken-ichiopen access© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalAstrocyteNoradrenalineAdrenoceptorInterleukin-6MAPK649In brain astrocytes, noradrenaline (NA) has been shown to up-regulate IL-6 production via 13-adrenoceptors (ARs). However, the underlying intracellular mechanisms for this regulation are not clear, and it remains unknown whether ?-ARs are involved. In this study, we investigated the AR-mediated regulation of IL-6 mRNA levels in the cultured astrocytes from rat spinal cord. NA, the ?1-agonist phenylephrine, and the 13-agonist isoproterenol increased IL-6 mRNA levels. The phenylephrine-induced IL-6 increase was accompanied by an increase in ERK phosphorylation, and these effects were blocked by inhibitors of PKC and ERK. The isoproterenol-induced IL-6 increase was accompanied by an increase in CREB phosphorylation, and these effects were blocked by a PKA inhibitor. Our results indicate that IL-6 increases by ?1- and 13-ARs are mediated via the PKC/ERK and cAMP/PKA/CREB pathways, respectively. Moreover, conditioned medium collected from astrocytes treated with the ?2-AR agonist dexmedetomidine, increased IL-6 mRNA in other astrocytes. In this study, we elucidate that ?1- and ?2-ARs, in addition to 13-ARs, promote IL-6 transcription through different pathways in spinal cord astrocytes.Elsevier2021-06-01engjournal articleAMhttp://hdl.handle.net/2115/85642https://doi.org/10.1016/j.cyto.2021.1554971043-4666Cytokine142155497https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/85642/1/Cytokine142_155497.pdfapplication/pdf2.21 MB2021-06-01