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Interleukin‐6‐mediated signaling in adrenal medullary chromaffin cells
Author(s) -
Jenkins Danielle E.,
Sreenivasan Dharshini,
Carman Fiona,
Samal Babru,
Eiden Lee E.,
Bunn Stephen J.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13870
Subject(s) - biology , endocrinology , tyrosine phosphorylation , medicine , adrenal medulla , signal transduction , microbiology and biotechnology , catecholamine
The pro‐inflammatory cytokines, tumor necrosis factor‐α, and interleukin‐1β/α modulate catecholamine secretion, and long‐term gene regulation, in chromaffin cells of the adrenal medulla. Since interleukin‐6 ( IL 6) also plays a key integrative role during inflammation, we have examined its ability to affect both tyrosine hydroxylase activity and adrenomedullary gene transcription in cultured bovine chromaffin cells. IL 6 caused acute tyrosine/threonine phosphorylation of extracellular signal‐regulated kinase 1/2 ( ERK 1/2), and serine/tyrosine phosphorylation of signal transducer and activator of transcription 3 ( STAT 3). Consistent with ERK 1/2 activation, IL 6 rapidly increased tyrosine hydroxylase phosphorylation (serine‐31) and activity, as well as up‐regulated genes, encoding secreted proteins including galanin, vasoactive intestinal peptide, gastrin‐releasing peptide, and parathyroid hormone‐like hormone. The effects of IL 6 on the entire bovine chromaffin cell transcriptome were compared to those generated by G‐protein‐coupled receptor ( GPCR ) agonists (histamine and pituitary adenylate cyclase‐activating polypeptide) and the cytokine receptor agonists (interferon‐α and tumor necrosis factor‐α). Of 90 genes up‐regulated by IL 6, only 16 are known targets of IL 6 in the immune system. Those remaining likely represent a combination of novel IL 6/ STAT 3 targets, ERK 1/2 targets and, potentially, IL 6‐dependent genes activated by IL 6‐induced transcription factors, such as hypoxia‐inducible factor 1α. Notably, genes induced by IL 6 include both neuroendocrine‐specific genes activated by GPCR agonists, and transcripts also activated by the cytokines. These results suggest an integrative role for IL 6 in the fine‐tuning of the chromaffin cell response to a wide range of physiological and paraphysiological stressors, particularly when immune and endocrine stimuli converge.