Tetracycline suppresses ATP gamma S-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 anti-microbial 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)gamma S, 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 ATP gamma S-induced release of pro-inflammatory mediators by HMEC-1 cells and primary human dermal microvascular endothelial cells. TCN dose-dependently inhibited ATP gamma S-induced augmentation of CXCL8 (interleukin-8) and CXCL1 (growth-regulated oncogene-alpha) production by HMEC-1 cells and primary human dermal endothelial cells in vitro. TCN and ATP gamma S 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.

• Authors: Anna Bender, Tamar Zapolanski, Shannon Watkins, Ava Khosraviani, Kristina Seiffert, Wanhong Ding, John A Wagner, Richard D Granstein
• Journal: Experimental dermatology (Exp Dermatol) Vol. 17 Issue 9 Pg. 752-60 (Sep 2008) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 18341570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Anti-Inflammatory Agents
• Chemokine CXCL1
• Interleukin-8
• Penicillins
• Protein Synthesis Inhibitors
• Tumor Necrosis Factor-alpha
• adenosine 5'-O-(3-thiotriphosphate)
• Adenosine Triphosphate
• Tetracycline
• Hydrocortisone

Topics

• Adenosine Triphosphate (analogs & derivatives, pharmacology)
• Anti-Bacterial Agents (pharmacology)
• Anti-Inflammatory Agents (pharmacology)
• Cell Line, Transformed
• Cell Survival (drug effects)
• Chemokine CXCL1 (metabolism)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, metabolism)
• Humans
• Hydrocortisone (pharmacology)
• Interleukin-8 (metabolism)
• Microvessels (cytology)
• Penicillins (pharmacology)
• Protein Synthesis Inhibitors (pharmacology)
• Skin (blood supply, cytology)
• Tetracycline (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)