Tetracycline suppresses ATPγS‐induced CXCL8 and CXCL1 production by the human dermal microvascular endothelial cell‐1 (HMEC‐1) cell line and primary human dermal microvascular endothelial cells

Abstract

Tetracyclines (TCN) have powerful anti-inflammatory properties in addition to their antimicrobial effects. These anti-inflammatory effects are thought to play a role in inhibiting cutaneous inflammation in patients with rosacea and acne; however, the mechanism(s) of this action remains poorly understood. We have previously shown that adenosine-5′-triphosphate (ATP)γS, a hydrolysis-resistant ATP analogue, augments secretion of pro-inflammatory messengers by a human dermal microvascular endothelial cell line (HMEC-1). ATP released by the sympathetic nerves during stress may stimulate release of pro-inflammatory chemokines by dermal vessel endothelial cells, resulting in recruitment of inflammatory cells and exacerbation of inflammatory skin disease. Here we demonstrate that TCN inhibits ATPγS-induced release of proinflammatory mediators by HMEC-1 cells and primary human dermal microvascular endothelial cells. TCN dose-dependently inhibited ATPγS-induced augmentation of CXCL8 (interleukin-8) and CXCL1 (growth-regulated oncogene-α) production by HMEC-1 cells and primary human dermal endothelial cells in vitro. TCN and ATPγS did not affect HMEC-1 cell viability as determined by trypan-blue exclusion and cell counts. Inhibition of production of inflammatory mediators by endothelial cells may be one mechanism by which TCN improves inflammatory skin diseases. The ability to inhibit release of inflammatory mediators induced in HMEC-1 cells by purinergic agonists may be a useful way to screen for potential therapeutic agents for cutaneous inflammation.

Dexamethasone Enhances ATP-Induced Inflammatory Responses in Endothelial Cells

“…Dexamethasone causes a rapid (e.g., 0.5-6 h) but transient up-regulation of P2Y 2 R mRNA in murine thymocytes (Koshiba et al, 1997). Hydrocortisone inhibited adenosine 5Ј-(␥-thiotriphosphate) induction of CXCL8 (IL-8) in HMEC-1 endothelial cells when coincubated for 24 h, suggesting that the interval between glucocorticoid and ATP exposure may be important in subsequent responses (Bender et al, 2008). Nongenomic effects of glucocorticoids on purinergic signaling have been described in a variety of cell types.…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…Intra-arterial infusion of ATP, ADP, and AMP in canine facial and nasal vascular Purinergic Signaling and Blood Vessels beds caused vasodilation (Bari et al, 1993). Purinergic agonists [ATP and adenosine-59-(g-thio)-triphosphate (ATPgS)] induce release of inflammatory mediators from human dermal microvascular endothelial cells (Bender et al, 2008). ATP and NA synergize in inducing IL-6 production by human dermal microvascular endothelial cells (Stohl et al, 2010).…”

Purinergic Signaling in Healthy and Diseased Skin

“…A recent paper claimed that UV radiation evokes ATP release from keratinocytes and that P2Y 6 receptors mediate UV radiation-induced inflammatory responses of keratinocytes (Takai et al, 2011). Purinergic agonists (ATP and ATPgS) induce release of inflammatory mediators from human dermal microvascular endothelial cells (Bender et al, 2008). Intradermal administration of ATPgS results in an enhanced contact hypersensitivity response in mice, and it was suggested ''that ATP, when released after trauma or infection, may act as an endogenous adjuvant to enhance the immunoresponse and that P2 receptor agonists may augment the efficacy of vaccines'' (Granstein et al, 2005).…”