Back to Search
Start Over
Inflammatory Responses in Embryonal Cardiomyocytes Exposed to LPS Challenge. An In Vitro Model of Deciphering the Effects of LPS on the Heart
- Source :
- Current Pharmaceutical Design. 16:754-765
- Publication Year :
- 2010
- Publisher :
- Bentham Science Publishers Ltd., 2010.
-
Abstract
- This study is focused on the links between the major products of inflammation and cell damage induced by the administration of lipopolysaccharide (LPS) from Salmonella typhimurium in embryonal cardiomyocytes. LPS treatment for 72 hours induced transcription factor NF-kappaB activation, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression, nitric oxide (NO) and tumor necrosis factor (TNF)-alpha release. Moreover, LPS administration induced a significant cell loss, reversed by the NO-synthases inhibitor, suggesting a relationship between cell damage and iNOS-dependent NO overproduction. Cell death was reversed by the specific NF-kappaB inhibitor, TPCK, whereas COX-2 specific inhibitor determined an increase of cell damage in terms of apoptosis, as observed by YO-PRO immunostaining, DNA laddering analysis and caspase-3 activation. Overall these findings evidenced a selective role for NF-kappaB in mediating NO-induced cell damage and a protective action by COX-2 in LPS-treated embryonal cardiomyocytes. The reflection of these experiments on human cardiac pathology will be discussed.
- Subjects :
- Lipopolysaccharides
medicine.medical_specialty
Programmed cell death
Nitric Oxide Synthase Type II
Apoptosis
Inflammation
Chick Embryo
In Vitro Techniques
Pharmacology
DNA laddering
Nitric Oxide
Nitric oxide
chemistry.chemical_compound
Internal medicine
Drug Discovery
medicine
Animals
Myocytes, Cardiac
Enzyme Inhibitors
Cell damage
Cells, Cultured
biology
Caspase 3
Tumor Necrosis Factor-alpha
Tosylphenylalanyl Chloromethyl Ketone
NF-kappa B
Heart
medicine.disease
Nitric oxide synthase
Endocrinology
chemistry
Cyclooxygenase 2
biology.protein
Tumor necrosis factor alpha
medicine.symptom
Signal Transduction
Subjects
Details
- ISSN :
- 13816128
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Current Pharmaceutical Design
- Accession number :
- edsair.doi.dedup.....e4307b679144268d28ca57ec1be5543d