Cytokine‐mediated regulation of catecholamine biosynthesis in adrenal chromaffin cells (876.5)

Abstract

Catecholamines, neurohormones with extensive functions in the sympathetic regulation of blood pressure, have a well‐established role in cardiovascular disease and hypertension. Epidemiological data has shown that, in addition to elevations in the catecholamine adrenaline, hypertensive patients demonstrate altered plasma cytokine profiles, suggesting that hypertension entails a complex interplay of the neuroendocrine and immune systems. From preliminary work, we have found that spontaneously hypertensive rats (SHR) exhibit higher plasma levels of the cytokine CCL2, and decreased levels of interleukin (IL)‐1β and interferon (IFN)‐δ, compared to their normotensive counterparts. To delineate the relationship between cytokine‐mediated signalling and catecholamine synthesis, we tested a panel of cytokines for their ability to affect the expression of tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH) and phenylethanolamine N‐methyltransferase (PNMT), key enzymes for catecholamine biosynthesis. Adrenal medulla derived PC12 cells were treated with the cytokines IL‐1β, IL‐2, IL‐6, IL‐10, tumor necrosis factor‐α, IFN‐α, transforming growth factor‐β1, or CCL2, and transcriptional changes were analyzed using RT‐PCR. Alterations in the transcripts of TH, DBH and PNMT upon cytokine treatments were observed illustrating cytokine‐mediated regulation of catecholamine biosynthesis. Grant Funding Source: Supported by NSERC and CIHR