INVOLVEMENT OF MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAYS IN THE NUCLEAR RESPONSES AND CYTOKINE PRODUCTION INDUCED BY SALMONELLA-TYPHIMURIUMIN CULTURED INTESTINAL EPITHELIAL-CELLS
S. Hobbie et al., INVOLVEMENT OF MITOGEN-ACTIVATED PROTEIN-KINASE PATHWAYS IN THE NUCLEAR RESPONSES AND CYTOKINE PRODUCTION INDUCED BY SALMONELLA-TYPHIMURIUMIN CULTURED INTESTINAL EPITHELIAL-CELLS, The Journal of immunology, 159(11), 1997, pp. 5550-5559
Central to the pathogenesis of Salmonella typhimurium is its ability t
o engage the host cell in a two-way biochemical interaction. As a cons
equence of this interaction, a dedicated protein secretion system, ter
med type III, is activated in these bacteria and directs-the transloca
tion of signaling proteins into the host cell, Secretion of these prot
eins stimulates host cell signal transduction pathways that lead to a
variety of cellular responses, An important feature of S. typhimurium
pathogenesis is the induction of a profound inflammatory response in t
he intestinal epithelium. in this report, we show that S. typhimurium
induces host cell signal transduction pathways hat lead to the activat
ion of the transcription factors NF-kappa B and AP-1, resulting in the
production of proinflammatory cytokines such as IL-8, We also show th
at S. typhimurium infection of cultured intestinal epithelial cells re
sults in the activation of the mitogen-activated protein (MAP) kinases
ERK, JNK, and p38, induction of these signaling pathways and the synt
hesis of IL-8 was strictly dependent on the function of the invasion-a
ssociated type III protein secretion system encoded by S. typhimurium.
Pretreatment of cells with the highly specific p38 MAP kinase inhibit
or SB 203580 prevented S. typhimurium-induced IL-8 production, These r
esults indicate that the inflammatory response induced by S. typhimuri
um. may be due to the specific stimulation of MAP kinase signaling pat
hways leading to nuclear responses.