Coordinate activation of activator protein 1 and inflammatory cytokines in response to Neisseria gonorrhoeae epithelial cell contact involves stress response kinases. Academic Article uri icon

Overview

abstract

  • Neisseria gonorrhoeae (Ngo), the etiologic agent of gonorrhea, induce a number of proinflammatory cytokines by contact to epithelial cells. Cytokine genes and a variety of other immune response genes are activated as a result of the regulatory function of immediate early response transcription factors including activator protein 1 (AP-1). Since it is established that phosphorylation of c-Jun, the central component of AP-1, by the stress-activated c-Jun NH2-terminal kinase (JNK) increases the transcriptional activity of AP-1, we studied whether Ngo could induce stress response pathways involving JNK. We found that virulent Ngo strains induce phosphorylation and activation of JNK but not of p38 kinase. Analysis of a nonpathogenic Ngo strain revealed only weak JNK activation. In respect to the molecular components upstream of the JNK signaling cascade, we show that a dominant negative mutant of MAP kinase kinase 4 (MKK4) represses transcription of an AP-1-dependent reporter gene. Regarding upstream stress response factors involved in Ngo-induced MKK4/JNK/AP-1 activation, we identified p21-activated kinase (PAK) but not MAPK/ERK kinase kinase (MEKK1). Inhibition of small GTPases including Rac1 and Cdc42 by Toxin B prevented JNK and AP-1 activation. Our results indicate that Ngo induce the activation of proinflammatory cytokines via a cascade of cellular stress response kinases involving PAK, which directs the signal from the Rho family of small GTPases to JNK/AP-1 activation.

publication date

  • October 5, 1998

Research

keywords

  • Bacterial Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cytokines
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases
  • Neisseria gonorrhoeae
  • Protein Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Transcription Factor AP-1

Identity

PubMed Central ID

  • PMC2212490

Scopus Document Identifier

  • 0032487573

Digital Object Identifier (DOI)

  • 10.1084/jem.188.7.1277

PubMed ID

  • 9763607

Additional Document Info

volume

  • 188

issue

  • 7