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Published on: September 17, 2015
Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts
1Carl-Ludwig-Institut für Physiologie, Universität Leipzig, D-04103 Leipzig, Germany.
Insights
Norepinephrine significantly increases interleukin-6 (IL-6) production in rat cardiac fibroblasts, suggesting IL-6 may contribute to cardiac hypertrophy and heart disease. Carvedilol blocks this effect.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Physiology
Background:
- Proinflammatory cytokines are key in heart disease pathophysiology.
- Interleukin-6 (IL-6) is implicated in cardiac hypertrophy mechanisms.
- Catecholamines are known inducers of cardiac hypertrophy.
Purpose of the Study:
- Investigate cardiac fibroblasts as a source of IL-6 in rat hearts.
- Determine if catecholamines modulate IL-6 synthesis in cardiac fibroblasts.
Main Methods:
- Quantified IL-6 mRNA in rat cardiac fibroblasts.
- Stimulated fibroblasts with norepinephrine (NE), phenylephrine, and isoproterenol.
- Assessed the effect of carvedilol, an adrenergic antagonist.
Main Results:
- Basal IL-6 mRNA levels in unstimulated fibroblasts were low.
- Norepinephrine (NE) induced a 50-fold increase in IL-6 mRNA.
- Alpha- and beta-adrenergic agonists increased IL-6; beta-receptor stimulation was more potent.
- Carvedilol inhibited NE-induced IL-6 mRNA synthesis.
Conclusions:
- Norepinephrine stimulates IL-6 expression in rat cardiac fibroblasts.
- IL-6 may play an autocrine/paracrine role in cardiac hypertrophy.
- Adrenergic signaling pathways influence IL-6 production in the heart.
Abstract:
Proinflammatory cytokines have been implicated in the pathophysiology of different heart diseases. Recent evidence suggests that interleukin-6 (IL--6) may play a role in mechanisms leading to cardiac hypertrophy. In addition, catecholamines are known to induce cardiac hypertrophy. In the present study, we examined whether cardiac fibroblasts may be a potential source of IL--6 production in the rat heart and whether catecholamines can modulate the IL--6 synthesis. Only a small amount of IL--6 mRNA was detected in unstimulated rat cardiac fibroblasts. However, a 50-fold increase of IL--6 mRNA was found after stimulation with norepinephrine (NE). Addition of carvedilol, a alpha- and beta-adrenergic receptor antagonist, prevented almost completely the NE-induced synthesis of IL--6 mRNA. Phenylephrine, an alpha-adrenergic agonist, and isoproterenol, a beta-adrenergic agonist, also induced an increase in IL--6. However, the stimulation via beta-receptors led to a more pronounced elevation. These data show that NE increases IL--6 expression in rat cardiac fibroblasts and that IL--6 may play an important autocrine/paracrine role in cardiac disease states associated with hypertrophy.

