Author(s): Mogensen Trine | Berg Randi | Østergaard Lars | Paludan Søren
Journal: BMC Immunology
ISSN 1471-2172
Volume: 9;
Issue: 1;
Start page: 52;
Date: 2008;
Original page
ABSTRACT
Abstract Background Streptococcus pneumoniae is a human pathogenic bacteria and a major cause of severe invasive diseases, including pneumonia, bacteremia, and meningitis. Infections with S. pneumoniae evoke a strong inflammatory response, which plays a major role in the pathogenesis of pneumococcal disease. Results In this study, we have examined how S. pneumoniae affects expression of the inflammatory cytokine tumor necrosis factor (TNF) α, and the molecular mechanisms involved. Secretion of TNF-α was strongly induced by S. pneumoniae, which was able to stabilize TNF-α mRNA through a mechanism dependent on the viability of the bacteria as well as the adenylate uridylate-rich elements in the 3'untranslated region of TNF-α mRNA. The ability of S. pneumoniae to stabilize TNF-α mRNA was dependent on the mitogen-activated protein kinase (MAPK) p38 whereas inhibition of Toll-like receptor signaling via MyD88 did not affect S. pneumoniae-induced mRNA stabilization. P38 was activated through a pathway involving the upstream kinase transforming growth factor-activated kinase 1 and MAPK kinase 3. Conclusion Thus, S. pneumoniae stabilizes TNF-α mRNA through a pathway dependent on p38 but independent of Toll-like receptors. Production of TNF-α may contribute significantly to the inflammatory response raised during pneumococcal infection.
Journal: BMC Immunology
ISSN 1471-2172
Volume: 9;
Issue: 1;
Start page: 52;
Date: 2008;
Original page
ABSTRACT
Abstract Background Streptococcus pneumoniae is a human pathogenic bacteria and a major cause of severe invasive diseases, including pneumonia, bacteremia, and meningitis. Infections with S. pneumoniae evoke a strong inflammatory response, which plays a major role in the pathogenesis of pneumococcal disease. Results In this study, we have examined how S. pneumoniae affects expression of the inflammatory cytokine tumor necrosis factor (TNF) α, and the molecular mechanisms involved. Secretion of TNF-α was strongly induced by S. pneumoniae, which was able to stabilize TNF-α mRNA through a mechanism dependent on the viability of the bacteria as well as the adenylate uridylate-rich elements in the 3'untranslated region of TNF-α mRNA. The ability of S. pneumoniae to stabilize TNF-α mRNA was dependent on the mitogen-activated protein kinase (MAPK) p38 whereas inhibition of Toll-like receptor signaling via MyD88 did not affect S. pneumoniae-induced mRNA stabilization. P38 was activated through a pathway involving the upstream kinase transforming growth factor-activated kinase 1 and MAPK kinase 3. Conclusion Thus, S. pneumoniae stabilizes TNF-α mRNA through a pathway dependent on p38 but independent of Toll-like receptors. Production of TNF-α may contribute significantly to the inflammatory response raised during pneumococcal infection.
