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

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.