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Interleukin-6-mediated signaling in adrenal medullary chromaffin cells
| Content Provider | Scilit |
|---|---|
| Author | Jenkins, Danielle E. Sreenivasan, Dharshini Carman, Fiona Samal, Babru Eiden, Lee E. Bunn, Stephen J. |
| Copyright Year | 2016 |
| Description | Journal: Journal of Neurochemistry 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 (IL6) 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. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine/tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). Consistent with ERK1/2 activation, IL6 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 IL6 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 IL6, only 16 are known targets of IL6 in the immune system. Those remaining likely represent a combination of novel IL6/STAT3 targets, ERK1/2 targets and, potentially, IL6-dependent genes activated by IL6-induced transcription factors, such as hypoxia-inducible factor 1α. Notably, genes induced by IL6 include both neuroendocrine-specific genes activated by GPCR agonists, and transcripts also activated by the cytokines. These results suggest an integrative role for IL6 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177545/pdf |
| Ending Page | 1150 |
| Page Count | 13 |
| Starting Page | 1138 |
| e-ISSN | 14714159 |
| DOI | 10.1111/jnc.13870 |
| Journal | Journal of Neurochemistry |
| Issue Number | 6 |
| Volume Number | 139 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2016-12-05 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Tyrosine Hydroxylase |
| Content Type | Text |
| Resource Type | Article |
