title: Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin-1beta: role of neuropeptide Y and nitric oxide.
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-1beta (IL-1beta) on catecholamine release and synthesis from primary cell cultures of human adrenal chromaffin cells. The effect of IL-1beta on neuropeptide Y (NPY) release and the intracellular pathways involved in catecholamine release evoked by IL-1beta and NPY were also investigated. We observed that IL-1beta 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-1beta. Moreover, IL-1beta regulates catecholamine synthesis as the inhibition of tyrosine hydroxylase decreases IL-1beta-evoked catecholamine release and the cytokine induces tyrosine hydroxylase Ser40 phosphorylation. Moreover, IL-1beta 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-1beta, 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.
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Rosmaninho-Salgado
authors.forename: Inês M
authors.initials: IM
authors.lastname: Araújo
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Alvaro
authors.forename: Alexandrina F
authors.initials: AF
authors.lastname: Mendes
authors.forename: Lígia
authors.initials: L
authors.lastname: Ferreira
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.forename: Emília P
authors.initials: EP
authors.lastname: Duarte
authors.forename: Cláudia
authors.initials: C
authors.lastname: Cavadas
mesh_terms: D000311:Adrenal Glands / Q000166:cytology*; D000704:Analysis of Variance; D000906:Antibodies / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009478:Neuropeptide Y / Q000276:immunology / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000906:Antibodies; D002395:Catecholamines; D004791:Enzyme Inhibitors; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D009478:Neuropeptide Y; D009569:Nitric Oxide; D014446:Tyrosine 3-Monooxygenase; D019331:NG-Nitroarginine Methyl Ester