Immune-neuroendocrine Integration at the Adrenal Gland: Cytokine Control of the Adrenomedullary Transcriptome

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2012 Mar 17

PMID 22421803

Citations 9

Authors

Stephen J Bunn

Djida Ait-Ali

Lee E Eiden

Affiliations

Soon will be listed here.

Abstract

The bovine chromaffin cell represents an ideal model for the study of cell signaling to gene expression by first messengers. An abundance of GPCR, ionotropic, and growth factor receptors are expressed on these cells, and they can be obtained and studied as an abundant highly enriched cell population; importantly, this is true of no other postmitotic neuroendocrine or neuronal cell type. Chromaffin cells have now been shown to bear receptors for cytokines whose expression in the circulation is highly elevated in inflammation, including tumor necrosis factor, interferon, interleukin-1, and interleukin-6. The use of bovine-specific microarrays, and various biochemical measurements in this highly homogenous cell preparation reveals unique cohorts of distinct genes regulated by cytokines in chromaffin cells, via signaling pathways that are in some cases uniquely neuroendocrine. The transcriptomic signatures of cytokine signaling in chromaffin cells suggest that the adrenal medulla may integrate neuronal, hormonal, and immune signaling during inflammation, through induction of paracrine factors that signal to both adrenal cortex and sensory afferents of the adrenal gland, and autocrine factors, which determine the duration and type of paracrine secretory signaling that occurs in either acute or chronic inflammatory conditions.

Citing Articles

Neurotensin via Type I Receptor Modulates the Endotoxemia Induced Oxido-Inflammatory Stress on the Sympathetic Adrenomedullary System of Mice Regulating NF-κβ/Nor-Epinephrine Pathway.

Tiwari A, Mohanty B Cell Biochem Biophys. 2025; .

PMID: 39881060 DOI: 10.1007/s12013-025-01679-5.

JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.

Sarapultsev A, Gusev E, Komelkova M, Utepova I, Luo S, Hu D Mol Biomed. 2023; 4(1):40.

PMID: 37938494 PMC: 10632324. DOI: 10.1186/s43556-023-00151-1.

Exercise-induced α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation.

Yuan Y, Xu P, Jiang Q, Cai X, Wang T, Peng W EMBO J. 2020; 39(7):e103304.

PMID: 32104923 PMC: 7110140. DOI: 10.15252/embj.2019103304.

What's New in Endocrinology: The Chromaffin Cell.

Eiden L, Jiang S Front Endocrinol (Lausanne). 2018; 9:711.

PMID: 30564193 PMC: 6288183. DOI: 10.3389/fendo.2018.00711.

Tyrosine-hydroxylase immunoreactivity in the mouse transparent brain and adrenal glands.

Godefroy D, Rostene W, Anouar Y, Reaux-Le Goazigo A J Neural Transm (Vienna). 2018; 126(4):367-375.

PMID: 30206700 DOI: 10.1007/s00702-018-1925-x.

References

Gwosdow A . Mechanisms of interleukin-1-induced hormone secretion from the rat adrenal gland. Endocr Res. 1995; 21(1-2):25-37. DOI: 10.3109/07435809509030418. View

Ait-Ali D, Samal B, Mustafa T, Eiden L . Neuropeptides, growth factors, and cytokines: a cohort of informational molecules whose expression is up-regulated by the stress-associated slow transmitter PACAP in chromaffin cells. Cell Mol Neurobiol. 2010; 30(8):1441-9. PMC: 4183212. DOI: 10.1007/s10571-010-9620-y. View

Bertini R, Bianchi M, Ghezzi P . Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J Exp Med. 1988; 167(5):1708-12. PMC: 2188949. DOI: 10.1084/jem.167.5.1708. View

Elenkov I, Wilder R, Chrousos G, Vizi E . The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000; 52(4):595-638. View

Eskay R, Eiden L . Interleukin-1 alpha and tumor necrosis factor-alpha differentially regulate enkephalin, vasoactive intestinal polypeptide, neurotensin, and substance P biosynthesis in chromaffin cells. Endocrinology. 1992; 130(4):2252-8. DOI: 10.1210/endo.130.4.1372239. View

Ait-Ali D, Turquier V, Grumolato L, Yon L, Jourdain M, Alexandre D . The proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 stimulate neuropeptide gene transcription and secretion in adrenochromaffin cells via activation of extracellularly regulated kinase 1/2 and p38 protein kinases, and.... Mol Endocrinol. 2004; 18(7):1721-39. DOI: 10.1210/me.2003-0129. View

Weihe E, Nohr D, Michel S, Muller S, Zentel H, Fink T . Molecular anatomy of the neuro-immune connection. Int J Neurosci. 1991; 59(1-3):1-23. DOI: 10.3109/00207459108985446. View

Rosmaninho-Salgado J, Alvaro A, Grouzmann E, Duarte E, Cavadas C . Neuropeptide Y regulates catecholamine release evoked by interleukin-1beta in mouse chromaffin cells. Peptides. 2007; 28(2):310-4. DOI: 10.1016/j.peptides.2006.11.015. View

Ait-Ali D, Turquier V, Tanguy Y, Thouennon E, Ghzili H, Mounien L . Tumor necrosis factor (TNF)-alpha persistently activates nuclear factor-kappaB signaling through the type 2 TNF receptor in chromaffin cells: implications for long-term regulation of neuropeptide gene expression in inflammation. Endocrinology. 2008; 149(6):2840-52. PMC: 2408812. DOI: 10.1210/en.2007-1192. View

10.

Tweedie D, Sambamurti K, Greig N . TNF-alpha inhibition as a treatment strategy for neurodegenerative disorders: new drug candidates and targets. Curr Alzheimer Res. 2007; 4(4):378-85. DOI: 10.2174/156720507781788873. View

11.

Morita K, Miyasako T, Kitayama S, Dohi T . Interleukin-1 inhibits voltage-dependent P/Q-type Ca2+ channel associated with the inhibition of the rise of intracellular free Ca2+ concentration and catecholamine release in adrenal chromaffin cells. Biochim Biophys Acta. 2004; 1673(3):160-9. DOI: 10.1016/j.bbagen.2004.04.012. View

12.

Weihe E, Nohr D, Muller S, Buchler M, Friess H, Zentel H . The tachykinin neuroimmune connection in inflammatory pain. Ann N Y Acad Sci. 1991; 632:283-95. DOI: 10.1111/j.1749-6632.1991.tb33116.x. View

13.

Andreis P, Tortorella C, Ziolkowska A, Spinazzi R, Malendowicz L, Neri G . Evidence for a paracrine role of endogenous adrenomedullary galanin in the regulation of glucocorticoid secretion in the rat adrenal gland. Int J Mol Med. 2007; 19(3):511-5. View

14.

Tortorella C, Neri G, Nussdorfer G . Galanin in the regulation of the hypothalamic-pituitary-adrenal axis (Review). Int J Mol Med. 2007; 19(4):639-47. View

15.

Gadient R, Lachmund A, Unsicker K, Otten U . Expression of interleukin-6 (IL-6) and IL-6 receptor mRNAs in rat adrenal medulla. Neurosci Lett. 1995; 194(1-2):17-20. DOI: 10.1016/0304-3940(95)11708-5. View

16.

Douglas S, Bunn S . 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. J Neuroendocrinol. 2009; 21(3):200-7. DOI: 10.1111/j.1365-2826.2009.01821.x. View

17.

Path G, Bornstein S, Ehrhart-Bornstein M, Scherbaum W . Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expression and effects on steroidogenesis. J Clin Endocrinol Metab. 1997; 82(7):2343-9. DOI: 10.1210/jcem.82.7.4072. View

18.

Elenkov I . Neurohormonal-cytokine interactions: implications for inflammation, common human diseases and well-being. Neurochem Int. 2007; 52(1-2):40-51. DOI: 10.1016/j.neuint.2007.06.037. View

19.

Thommesen L, Laegreid A . Distinct differences between TNF receptor 1- and TNF receptor 2-mediated activation of NFkappaB. J Biochem Mol Biol. 2005; 38(3):281-9. DOI: 10.5483/bmbrep.2005.38.3.281. View

20.

Douglas S, Sreenivasan D, Carman F, Bunn S . Cytokine interactions with adrenal medullary chromaffin cells. Cell Mol Neurobiol. 2010; 30(8):1467-75. PMC: 11498763. DOI: 10.1007/s10571-010-9593-x. View