YERSINIA-ENTEROCOLITICA PROMOTES DEACTIVATION OF MACROPHAGE MITOGEN-ACTIVATED PROTEIN-KINASES EXTRACELLULAR SIGNAL-REGULATED KINASE-1 2, P38, AND C-JUN NH2-TERMINAL KINASE - CORRELATION WITH ITS INHIBITORY EFFECT ON TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION/
K. Ruckdeschel et al., YERSINIA-ENTEROCOLITICA PROMOTES DEACTIVATION OF MACROPHAGE MITOGEN-ACTIVATED PROTEIN-KINASES EXTRACELLULAR SIGNAL-REGULATED KINASE-1 2, P38, AND C-JUN NH2-TERMINAL KINASE - CORRELATION WITH ITS INHIBITORY EFFECT ON TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION/, The Journal of biological chemistry, 272(25), 1997, pp. 15920-15927
The enteropathogenic bacterium Yersinia enterocolitica counteracts hos
t defense mechanisms by interfering with eukaryotic signal transductio
n pathways. In this study, we investigated the mechanism by which Y. e
nterocolitica prevents macrophage tumor necrosis factor-alpha (TNF alp
ha) production, Murine J774A.1 macrophages responded to Y. enterocolit
ica infection by rapid activation of mitogen activated protein kinases
(MAPK) extracellular signal-regulated kinase (ERK), p38, and c-Jun NH
2-terminal kinase (JNK), However, after initial activation, the virule
nt Y. enterocolitica strain harboring the Y. enterocolitica virulence
plasmid caused a substantial decrease in ERK1/2 and p38 tyrosine phosp
horylation, Simultaneously, the virulent Y. enterocolitica strain grad
ually suppressed phosphorylation of the transcription factors EIk-1, a
ctivating transcription factor 2 (ATF2), and c-Jun, indicating time-de
pendent inhibition of ERK1/2, p38, and JNK kinase activities, respecti
vely, Analysis of different Y. enterocolitica mutants revealed that (i
) MAPK inactivation parallels the inhibition of TNF alpha release, (ii
) the suppressor effect on TNF alpha production, which originates from
the lack of TNF alpha mRNA, is distinct from the ability of Y. entero
colitica to resist phagocytosis and to prevent the oxidative burst, (i
ii) the tyrosine phosphatase YopH, encoded by the Y. enterocolitica vi
rulence plasmid, is not involved in the decrease of ERK1/2 and p38 tyr
osine phosphorylation or in the cytokine suppressive effect. Altogethe
r, these results indicate that Y. enterocolitica possesses one or more
virulence proteins that suppress TNF alpha production by inhibiting E
RK1/2, p38, and JNK kinase activities.