title: Interferon-alpha signalling in bovine adrenal chromaffin cells: involvement of signal-transducer and activator of transcription 1 and 2, extracellular signal-regulated protein kinases 1/2 and serine 31 phosphorylation of tyrosine hydroxylase.
abstract: Adrenal medullary chromaffin cells are an integral part of the neuroendocrine system, playing an important role in the physiological adaptation to stress. In response to a wide variety of stimuli, including acetylcholine released from the splanchnic nerve, hormones such as angiotensin II or paracrine signals such as prostaglandins, chromaffin cells synthesise and secrete catecholamines and a number of biologically active peptides. This adrenal medullary output mediates a complex and diverse stress response. We report that chromaffin cells also respond both acutely and chronically to interferon (IFN)-alpha, thus providing a mechanism of interaction between the immune system and the stress response. Incubation of isolated bovine chromaffin cells maintained in culture, with IFN-alpha resulted in a rapid, transient activation of the extracellular signal-regulated protein kinase (ERK)1/2, which was maximal after 5 min. IFN-alpha mediated activation of ERK1/2 appeared to be responsible for the increased phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This tyrosine hydroxylase phosphorylation was exclusively on serine 31, with no change in the phosphorylation of serine 19 or 40. This increase in the serine 31 phosphorylation of tyrosine hydroxylase was prevented by inhibition of protein kinase C or ERK1/2 activation. Incubation with IFN-alpha also resulted in a time- and concentration-dependent phosphorylation and nuclear translocation of signal transducer and activator of transcription proteins (STAT)1 and 2. This response was maximal after approximately 60 min. Prolonged treatment with IFN-alpha (12-48 h) resulted in increased expression of STAT1 and, to a lesser extent, STAT2. Thus, these findings demonstrate that adrenal medullary chromaffin cells are responsive to IFN-alpha and provide a possible cellular mechanism by which this immune-derived signal can potentially influence and integrate with the stress response.
authors.affiliation: Centre for Neuroendocrinology and Department of Anatomy and Structural Biology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors.forename: S A
authors.initials: SA
authors.lastname: Douglas
authors.forename: S J
authors.initials: SJ
authors.lastname: Bunn
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D050795:STAT2 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D012694:Serine; D014446:Tyrosine 3-Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3