R-roscovitine Reduces Lung Inflammation Induced by Lipoteichoic Acid and Streptococcus pneumoniae
| Autor: | JanWillem Duitman, Catharina W. Wieland, Dana C. Blok, Tom van der Poll, Arie J. Hoogendijk, Joris J. T. H. Roelofs, Miriam H. P. van Lieshout |
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| Přispěvatelé: | Center of Experimental and Molecular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam institute for Infection and Immunity, Pathology, Cancer Center Amsterdam, Other departments, Infectious diseases, Intensive Care Medicine |
| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Neutrophils Apoptosis Inflammation Biology medicine.disease_cause Amino Acid Chloromethyl Ketones Cell Line Microbiology Proinflammatory cytokine Leukocyte Count Mice Streptococcus pneumoniae Roscovitine Genetics medicine Animals Humans Molecular Biology Genetics (clinical) medicine.diagnostic_test Caspase 3 Articles Pneumonia respiratory system medicine.disease Cyclin-Dependent Kinases respiratory tract diseases Mice Inbred C57BL Teichoic Acids Bronchoalveolar lavage Purines Alveolar macrophage Molecular Medicine Female Tumor necrosis factor alpha Lipoteichoic acid Chemokines Inflammation Mediators medicine.symptom Bronchoalveolar Lavage Fluid |
| Zdroj: | Molecular medicine (Cambridge, Mass.), 18(7), 1086-1095. Feinstein Institute for Medical Research |
| ISSN: | 1528-3658 1076-1551 |
| DOI: | 10.2119/molmed.2012.00033 |
| Popis: | Bacterial pneumonia remains associated with high morbidity and mortality. The gram-positive pathogen Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. Lipoteichoic acid (LTA) is an important proinflammatory component of the gram-positive bacterial cell wall. R-roscovitine, a purine analog, is a potent cyclin-dependent kinase (CDK)-1, -2, -5 and -7 inhibitor that has the ability to inhibit the cell cycle and to induce polymorphonuclear cell (PMN) apoptosis. We sought to investigate the effect of R-roscovitine on LTA-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LTA or viable S. pneumoniae in vivo. In vitro R-roscovitine enhanced apoptosis in PMNs and reduced tumor necrosis factor (TNF)-alpha and keratinocyte chemoattractant (KC) production in MH-S (alveolar macrophage) and MLE-12/MLE-15 (respiratory epithelial) cell lines. In vivo R-roscovitine treatment reduced PMN numbers in bronchoalveolar lavage fluid during LTA-induced lung inflammation; this effect was reversed by inhibiting apoptosis. Postponed treatment with R-roscovitine (24 and 72 h) diminished PMN numbers in lung tissue during gram-positive pneumonia; this step was associated with a transient increase in pulmonary bacterial loads. R-roscovitine inhibits proinflammatory responses induced by the gram-positive stimuli LTA and S. pneumoniae. R-roscovitine reduces PMN numbers in lungs upon LTA administration by enhancing apoptosis. The reduction in PMN numbers caused by R-roscovitine during S. pneumoniae pneumonia may hamper antibacterial defense. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00033 |
| Databáze: | OpenAIRE |
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