Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin-1β: role of neuropeptide Y and nitric oxide |
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Authors: | Joana Rosmaninho-Salgado Inês M Araújo Ana Rita Álvaro Alexandrina F Mendes† Lígia Ferreira Eric Grouzmann‡ Alfredo Mota§ Emília P Duarte¶ Cláudia Cavadas† |
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Institution: | Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Portugal; Division of Clinical Pharmacology and Toxicology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Urology and Renal Transplantation, Universitary Hospital of Coimbra, Coimbra, Portugal; Department of Zoology, University of Coimbra, Portugal |
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Abstract: | Adrenal chromaffin cells synthesize and secrete catecholamines and neuropeptides that may regulate hormonal and paracrine signaling in stress and also during inflammation. The aim of our work was to study the role of the cytokine interleukin-1β (IL-1β) on catecholamine release and synthesis from primary cell cultures of human adrenal chromaffin cells. The effect of IL-1β on neuropeptide Y (NPY) release and the intracellular pathways involved in catecholamine release evoked by IL-1β and NPY were also investigated. We observed that IL-1β increases the release of NPY, norepinephrine (NE), and epinephrine (EP) from human chromaffin cells. Moreover, the immunoneutralization of released NPY inhibits catecholamine release evoked by IL-1β. Moreover, IL-1β regulates catecholamine synthesis as the inhibition of tyrosine hydroxylase decreases IL-1β-evoked catecholamine release and the cytokine induces tyrosine hydroxylase Ser40 phosphorylation. Moreover, IL-1β induces catecholamine release by a mitogen-activated protein kinase (MAPK)-dependent mechanism, and by nitric oxide synthase activation. Furthermore, MAPK, protein kinase C (PKC), protein kinase A (PKA), and nitric oxide (NO) production are involved in catecholamine release evoked by NPY. Using human chromaffin cells, our data suggest that IL-1β, NPY, and nitric oxide (NO) may contribute to a regulatory loop between the immune and the adrenal systems, and this is relevant in pathological conditions such as infection, trauma, stress, or in hypertension. |
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Keywords: | catecholamine human chromaffin cells interleukin-1β neuropeptide Y nitric oxide tyrosine hydroxylase |
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