Azithromycin reduces Chlamydia pneumoniae-induced attenuation of eNOS and cGMP production by endothelial cells
| Autor: | W. E. Van Der Vlist, L. M. Bevers, R. J. A. Diepersloot, Frank L.J. Visseren, John J. M. Bouwman, K.P. Bouter |
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| Rok vydání: | 2005 |
| Předmět: |
Nitric Oxide Synthase Type III
Endothelium Cell Survival Clinical Biochemistry Azithromycin Pharmacology Biochemistry Nitric oxide chemistry.chemical_compound Enos medicine Humans Endothelial dysfunction Chlamydophila Infections Cyclic GMP Cyclic guanosine monophosphate Cells Cultured Antibacterial agent biology Endothelial Cells General Medicine Chlamydophila pneumoniae medicine.disease biology.organism_classification Anti-Bacterial Agents Nitric oxide synthase Endothelial stem cell medicine.anatomical_structure chemistry Cytomegalovirus Infections Immunology biology.protein Reactive Oxygen Species |
| Zdroj: | European Journal of Clinical Investigation. 35:573-582 |
| ISSN: | 1365-2362 0014-2972 |
| DOI: | 10.1111/j.1365-2362.2005.01541.x |
| Popis: | Intracellular infections with cytomegalovirus (CMV) or Chlamydia pneumoniae (Cp) may play a role in the aetiology of atherosclerosis. Nitric oxide (NO) is a key regulator of endothelial function. Under pathological conditions uncoupling of endothelial nitric oxide synthase (eNOS) leads to vessel damage as a result of production of oxygen radicals instead of NO. We hypothesized that infection-induced atherosclerosis is initiated by changes in NO metabolism and may be reversed by azithromycin treatment.Confluent human umbilical vein endothelial cells (HUVECs) were infected with Cp or CMV. After 48 h of infection, production of eNOS, cyclic guanosine monophosphate (cGMP) and reactive oxygen species (ROS) was measured. Detection of cGMP was used as a reporter assay for the bioavailability of NO. Subsequently, Cp- and CMV-infected HUVECs were coincubated with 0.016 mg L(-1) and 1 mg L(-1) azithromycin.Infection with Cp (MOI 1 and MOI 0.1) and CMV (MOI 1) caused a dose- and time-dependent reduction of eNOS production in the HUVECs: Cp MOI 1: 1141 +/- 74 pg mL(-1) (P0.01); Cp MOI 0.1: 3189 +/- 30 pg mL(-1) (P0.01); CMV: 3213 +/- 11 pg mL(-1) (P0.01) vs. 3868 +/- 83 pg mL(-1) for uninfected HUVECs. Chlamydia pneumoniae- but not CMV-infection also reduced cGMP-production (Cp: 0.195 +/- 0.030 pmol mL(-1) (P0.01); CMV: 0.371 +/- 27 pmol mL(-1) (P0.05) vs. 0.378 +/- 0.019 pmol mL(-1) for uninfected HUVECs). CMV-infection did not affect ROS production either, but Cp-infection reduced ROS-production by 21% (P0.05; Cp MOI 0.1) to 68% (P0.01; Cp MOI 1). Azithromycin treatment restored Cp-induced eNOS, cGMP and ROS production in a dose-dependent manner.Infection with Cp in endothelial cells in vitro attenuates eNOS, cGMP and ROS production in HUVECs and azithromycin reverses Cp-induced effects on eNOS, cGMP and ROS-production. The results from our in vitro research support the role of antibiotic therapy for infection-induced atherosclerosis by indicating that azithromycin does actually improve endothelial function. |
| Databáze: | OpenAIRE |
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