Adrenal hormone deprivation affects macrophage catecholamine metabolism and β₂‐adrenoceptor density, but not propranolol stimulation of tumour necrosis factor‐α production

Abstract

New Findings r What is the central question of this study?Glucocorticoids modulate extraglandular catecholamine metabolism and adrenoceptor expression in many cell types. Catecholamines modulate the production of inflammatory mediators by macrophages. It was hypothesized that adrenal hormones affect tumour necrosis factor-α production in rat macrophages by altering the autocrine/paracrine action of catecholamines. r What is the main finding and its importance?In rat macrophages, adrenalectomy increased tyrosine hydroxylase expression, decreased monoamine oxidase-A mRNA expression (due to the absence of adrenal catecholamines and glucocorticoids, respectively) and augmented β 2 -adrenoceptor expression (due to lack of adrenal catecholamines). However, notwithstanding these changes, propranolol treatment increased lipopolysaccharide-stimulated tumour necrosis factor-α production in macrophages from adrenalectomized and non-operated rats to a similar extent.Catecholamines modulate the production of inflammatory mediators by macrophages in an autocrine/paracrine manner. They also tune β 2 -adrenoceptor expression. Glucocorticoids influence catecholamine metabolism and adrenoceptor expression in many cell types. We hypothesized that adrenal hormones affect the production of tumour necrosis factor-α (TNF-α) and NO by macrophages by altering the modulatory influence of catecholamines. To prove the hypothesis, peritoneal exudate macrophages from propranolol-treated nonoperated and adrenalectomized rats and from corticosterone-supplemented adrenalectomized rats were examined for lipopolysaccharide-stimulated NO and TNF-α production in vitro and for expression of β 2 -adrenoceptors and major catecholamine-metabolizing enzymes. Glucocorticoid deprivation increased NO production by macrophages, whereas 4 days of propranolol treatment was ineffective in this respect. However, propranolol treatment, via β 2 -adrenoceptor blockade, increased production of TNF-α by macrophages in both nonoperated and adrenalectomized rats (showing dramatically enhanced TNF-α production due to a lack of circulating glucocorticoids) for the same value. The expression of β 2 -adrenoceptor was increased in peritoneal macrophages that were freshly isolated from non-operated, propranolol-treated and adrenalectomized rats (due to adrenal catecholamine deficiency). Propranolol did not affect macrophage β 2 -adrenoceptor expression in adrenalectomized rats.

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

“…Inhibition of the β-adrenergic receptor with the β-blocker propranolol, or depletion of adrenal catecholamines by adrenalectomy, led to increased LPS-induced tumor necrosis factor (TNF) α production in peritoneal macrophages [12]. Alveolar macrophages recovered from mice chronically treated with β-blockers produced more noradrenaline, interleukin (IL) 6 and TNFα following LPS treatment ex vivo [13].…”

“…Recent data suggest that catecholamines can auto-regulate their levels and function by controlling expression of both tyrosine hydroxylase as well as catecholamine receptors [12]. For instance, adrenal catecholamines contribute to the paracrine regulation of macrophage synthesis of catecholamines and expression of the β-adrenergic receptor.…”

Frontline Science: D1 dopaminergic receptor signaling activates the AMPK-bioenergetic pathway in macrophages and alveolar epithelial cells and reduces endotoxin-induced ALI

“…Besides a regulatory role in the "fight or flight" reflex, catecholamines also affect pro-and anti-inflammatory responses in immune cells and peripheral tissues, mediated by the variety and bioavailability of adrenergic and dopaminergic receptors [2][3][4]. For example, adrenergic proand anti-inflammatory signaling is dependent on the abundance of a and b receptors [5,6]. Besides adrenergic signaling, recent studies have underscored the importance of dopaminergic pathways in moderating inflammatory conditions in experimental models of organ injury [7,8].…”

Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels: Role of Atherosclerotic Disease Progression and Chronic Social Stress

“…It has been reported that TH is also expressed in non-neuronal cells such as lymphocytes, macrophages and other immune cells (25, 38). Similarly, it has been reported that synapsin is also found in some non-neuronal cells (e.g., osteoblasts (39) insulinoma cells (40), epithelial cells (41)), but it has not been reported in vascular or immune cells.…”