Cytokine-mediated regulation of catecholamine biosynthetic enzymes in adrenal chromaffin cells

Abstract

The immune system is increasingly recognized for its role in the genesis and progression of hypertension. Catecholamines function in the neuro-hormonal regulation of blood pressure and have a well-established link to hypertension. It was hypothesized that cytokine signalling within the adrenal medulla influences catecholamine biosynthesis, thereby potentially impacting blood pressure. This study reports that IFN-α, IL-1β, IL-2, IL-6, IL-10, TNF-α, and CCL2 affected transcript levels of tyrosine hydroxylase, dopamine β-hydroxylase, and phenylethanolamine N-methyltransferase (PNMT) in PC12 cells. Further, simultaneous treatment with dexamethasone or forskolin produced context-dependent changes in the transcripts, some of which corresponded to alterations in PNMT promoter activation, but not to localization of glucocorticoid receptor. Thus, cytokines exert transcriptional control over catecholamine biosynthetic enzymes and cytokine signalling is integrated with hormonal and neural regulatory mechanisms in PC12 cells. Changes in adrenal cytokines during hypertension may promote blood pressure elevation by influencing catecholamine biosynthesis.