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Streptococcus pneumoniae-induced p38 MAPK-dependent phosphorylation of RelA at the interleukin-8 promotor

Bernd Schmeck1, Janine Zahlten, Kerstin Moog

  • 1Department of Internal Medicine/Infectious Diseases, Charité, University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

The Journal of Biological Chemistry
|October 16, 2004
PubMed

Insights

Streptococcus pneumoniae infection activates NF-kappaB and p38 MAPK pathways in lung epithelial cells, driving chemokine production. P38 MAPK signaling is crucial for NF-kappaB-mediated gene transcription, impacting pneumonia pathogenesis.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Streptococcus pneumoniae is a leading cause of pneumonia and infectious disease mortality.
  • Mechanisms of target cell activation in pneumococcal infections are not well understood.
  • Lung epithelial cells form the first line of defense against respiratory pathogens.

Purpose of the Study:

  • To investigate the roles of NF-kappaB and p38 MAPK signaling pathways in lung epithelial cells during Streptococcus pneumoniae infection.
  • To elucidate the contribution of these pathways to chemokine synthesis and innate immune responses.

Main Methods:

  • Utilized human bronchial epithelial cells (BEAS-2B) and mouse lungs as models.
  • Infected cells and tissues with Streptococcus pneumoniae.
  • Assessed activation of NF-kappaB and p38 MAPK signaling pathways.
  • Measured chemokine (IL-8, keratinocyte-derived chemokine) and cytokine expression.
  • Employed chemical inhibitors (SB202190, SB203580) and RNA interference for p38 MAPK inhibition.
  • Analyzed NF-kappaB/RelA translocation, phosphorylation, and RNA polymerase II recruitment.

Main Results:

  • Pneumococcal infection activated both NF-kappaB and p38 MAPK pathways in lung epithelial cells and mouse lungs.
  • Activated p38 MAPK was essential for NF-kappaB-dependent gene transcription, including IL-8.
  • Inhibition of p38 MAPK reduced pneumococci-induced cytokine release and chemokine transcription.
  • p38 MAPK modulated p65 NF-kappaB-mediated transactivation by affecting RelA phosphorylation and RNA polymerase II recruitment.

Conclusions:

  • NF-kappaB and p38 MAPK signaling pathways are critical for lung epithelial cell activation and chemokine synthesis in response to Streptococcus pneumoniae.
  • p38 MAPK plays a key role in regulating NF-kappaB-dependent gene expression, contributing to the innate immune response against pneumococcal infection.

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