β-Adrenergic receptor modulation of wound repair

Pullar, Christine E.; Manabat-Hidalgo, Catherine G.; Bolaji, Ranti S.; Isseroff, Roslyn Rivkah

doi:10.1016/j.phrs.2008.07.012

Cited by 41 publications

(40 citation statements)

References 130 publications

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“…Therefore, β-blockers have a strong effect on keratinocytes in vitro: they enhance cell proliferation [23], cell migration [24] and accelerate re-epithelialization. The latter may be positively influenced due to the additional angionetic effects of β-blockers [25].…”

Section: Discussionmentioning

confidence: 99%

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Besser

Terberger

Bachmann

et al. 2019

Skin Pharmacol Physiol

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Background: The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in terms of wound healing is low. Objective: Based on a few differing studies, the idea arose that antihypertensives may have side effects on wound healing. Methods: Five antihypertensive drugs from different substance classes (metoprolol, amlodipine, ramipril, hydrochlorothiazide, candesartan) were investigated, in terms of possible impacts on cell metabolism and migration of human skin fibroblasts and keratinocytes. Additionally, histological and immunohistochemical analyses were performed in a 3-dimensional (3D) wound model addressing the influence on regeneration processes, such as cell migration, metabolic activity, apoptosis and epidermal thickness. Results: Hydrochlorothiazide and ramipril exerted inhibiting effects in nearly all analyses, interestingly, in serum equivalent doses. In contrast, candesartan and amlodipine induced slight positive effects in 2D as well as in 3D models. The previously described positive effects of β-blockers could only partially be confirmed by metoprolol. Antihypertensive drugs affected fibroblasts more than keratinocytes – whether positively or negatively. Conclusion: Antihypertensive drugs have an influence on keratinocytes and fibroblasts; they are not neutral. Candesartan has the most positive effects on skin cells. For angiotensin-converting enzyme inhibitors and thiazide diuretics, wound healing in a 3D model is delayed. β-Receptor blockers seem to improve wound healing to a small extent just like calcium channel blockers. These results should be evaluated in a clinical trial to verify their clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Besser

Terberger

Bachmann

et al. 2019

Skin Pharmacol Physiol

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“…(101) Local effects of β-blockade may also be due in part to the presence of β adrenergic receptors on MSCs and endothelial cells. (102) β-2 receptor blockade increases migration and proliferation of keratinocytes during wound epithelialization, accelerating epidermal barrier repair. (102) NE-depleted mice have increased wound angiogenesis, (103) and rats treated with propranolol demonstrate increased wound blood vessel density.…”

Section: Burns and Wound Healingmentioning

confidence: 99%

“…(102) β-2 receptor blockade increases migration and proliferation of keratinocytes during wound epithelialization, accelerating epidermal barrier repair. (102) NE-depleted mice have increased wound angiogenesis, (103) and rats treated with propranolol demonstrate increased wound blood vessel density. (104) Likewise, among human burn patients, propranolol use resulted in faster donor site healing times.…”

Section: Burns and Wound Healingmentioning

confidence: 99%

β-Blockade use for Traumatic Injuries and Immunomodulation

Loftus

Efron

Moldawer

et al. 2016

Shock

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Sympathetic nervous system activation and catecholamine release are important events following injury and infection. The nature and timing of different pathophysiologic insults have significant effects on adrenergic pathways, inflammatory mediators, and the host response. Beta adrenergic receptor blockers (β-blockers) are commonly used for treatment of cardiovascular disease but recent data suggests that the metabolic and immunomodulatory effects of β-blockers can expand their use. β-blocker therapy can reduce sympathetic activation and hypermetabolism as well as modify glucose homeostasis and cytokine expression. It is the purpose of this review to examine either the biologic basis for proposed mechanisms or to describe current available clinical evidence for the use of β-blockers in traumatic brain injury (TBI), spinal cord injury (SCI), hemorrhagic shock, acute traumatic coagulopathy, erythropoietic dysfunction, metabolic dysfunction, pulmonary dysfunction, burns, immunomodulation, and sepsis.

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“…These receptors have been proven to be implicated in the pathogeny of skin inflammatory diseases such as vitiligo, psoriasis and atopic dermatitis [13,16] and in the regulation of wound healing [17][18][19] . However, the participation of the dopaminergic pathways in the physiology of the skin immune system has not been studied so far.…”

mentioning

confidence: 99%

Dopamine Agonists Upregulate IL-6 and IL-8 Production in Human Keratinocytes

Parrado

Canellada

Gentile

et al. 2012

Neuroimmunomodulation

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Aim: Catecholamines regulate functions of the nervous, neuroendocrine and immune systems. Dopamine may modulate the activity of keratinocytes, which play a role in secreting cytokines and chemokines. The aim of this study was to evaluate the effect of dopaminergic agonists on the production of IL-6 and IL-8 by a non-tumoral human keratinocyte cell line (HaCaT). Methods: Cells were stimulated with dopamine and the D2 dopamine receptor agonist cabergoline. Levels of IL-6 and IL-8 in culture supernatants were then determined. Cell proliferation was also assessed. Assays were carried out in the presence or absence of the dopaminergic and β-adrenergic receptor antagonists (sulpiride and propranolol, respectively) and ascorbic acid. Results: Dopamine stimulated the production of IL-6 and IL-8 in a concentration-dependent manner. The effects observed on the secretion of IL-6 were more potent than those corresponding to IL-8 and were reduced by ascorbic acid. The dopamine-induced IL-6 secretion was partially reduced by sulpiride and abrogated by propranolol. The latter drug was able to block the effect of dopamine on the secretion of IL-8. The cabergoline-induced IL-6 release was reduced by sulpiride. Cell viability was not affected by any of the drugs. Conclusions: Dopaminergic agonists can stimulate keratinocytes to produce IL-6 and IL-8 which are related to inflammatory cutaneous processes. These effects are mediated by dopaminergic and β-adrenergic receptors and by receptor-independent oxidative mechanisms.

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β-Adrenergic receptor modulation of wound repair

Cited by 41 publications

References 130 publications

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

β-Blockade use for Traumatic Injuries and Immunomodulation

Dopamine Agonists Upregulate IL-6 and IL-8 Production in Human Keratinocytes

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