PMID- 17577053
OWN - NLM
STAT- MEDLINE
DCOM- 20070827
LR  - 20200403
IS  - 0022-2615 (Print)
IS  - 0022-2615 (Linking)
VI  - 56
IP  - Pt 7
DP  - 2007 Jul
TI  - Comparative analysis of host-cell signalling mechanisms activated in response to 
      infection with Rickettsia conorii and Rickettsia typhi.
PG  - 896-906
LID - 10.1099/jmm.0.47050-0 [doi]
AB  - The Gram-negative intracellular bacteria Rickettsia conorii and Rickettsia typhi 
      are the aetiological agents of Mediterranean spotted fever and endemic typhus, 
      respectively, in humans. Infection of endothelial cells (ECs) lining vessel 
      walls, and the resultant vascular inflammation and haemostatic alterations are 
      salient pathogenetic features of both of these rickettsial diseases. An important 
      consideration, however, is that dramatic differences in the intracellular 
      motility and accumulation patterns for spotted fever versus typhus group 
      rickettsiae have been documented, suggesting the possibility of unique and 
      potentially different interactions with host cells. This study characterized and 
      compared R. conorii- and R. typhi-mediated effects on cultured human ECs. The 
      DNA-binding activity of nuclear transcription factor-kappaB (NF-kappaB) and the 
      phosphorylation status of stress-activated p38 kinase were determined as 
      indicators of NF-kappaB and p38 activation. R. conorii infection resulted in a 
      biphasic activation of NF-kappaB, with an early increase in DNA-binding activity 
      at 3 h, followed by a later peak at 24 h. The activated NF-kappaB species were 
      composed mainly of RelA p65-p50 heterodimers and p50 homodimers. R. typhi 
      infection of ECs resulted in only early activation of NF-kappaB at 3 h, composed 
      primarily of p65-p50 heterodimers. Whilst R. conorii infection induced increased 
      phosphorylation of p38 kinase (threefold mean induction) with the maximal 
      response at 3 h, a considerably less-intense response peaking at about 6 h 
      post-infection was found with R. typhi. Furthermore, mRNA expression of the 
      chemokines interleukin (IL)-8 and monocyte chemoattractant protein-1 in ECs 
      infected with either Rickettsia species was higher than the corresponding 
      controls, but there were distinct differences in the secretion patterns for IL-8, 
      suggesting the possibility of involvement of post-transcriptional control 
      mechanisms or differences in the release from intracellular storage sites. Thus, 
      the intensity and kinetics of host-cell responses triggered by spotted fever and 
      typhus species exhibit distinct variations that could subsequently lead to 
      differences in the extent of endothelial activation and inflammation and serve as 
      important determinants of pathogenesis.
FAU - Rydkina, Elena
AU  - Rydkina E
AD  - Hematology-Oncology Unit, Department of Medicine, University of Rochester School 
      of Medicine and Dentistry, Rochester, NY 14642, USA.
FAU - Sahni, Abha
AU  - Sahni A
AD  - Hematology-Oncology Unit, Department of Medicine, University of Rochester School 
      of Medicine and Dentistry, Rochester, NY 14642, USA.
FAU - Silverman, David J
AU  - Silverman DJ
AD  - Department of Microbiology and Immunology, University of Maryland School of 
      Medicine, Baltimore, MD 21201, USA.
FAU - Sahni, Sanjeev K
AU  - Sahni SK
AD  - Hematology-Oncology Unit, Department of Medicine, University of Rochester School 
      of Medicine and Dentistry, Rochester, NY 14642, USA.
LA  - eng
GR  - AI 040689/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Med Microbiol
JT  - Journal of medical microbiology
JID - 0224131
RN  - 0 (Chemokines)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokines/metabolism
MH  - Endothelial Cells/immunology/*microbiology
MH  - Humans
MH  - NF-kappa B/metabolism
MH  - Rickettsia conorii/immunology/*pathogenicity
MH  - Rickettsia typhi/immunology/*pathogenicity
MH  - *Signal Transduction/immunology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2007/06/20 09:00
MHDA- 2007/08/28 09:00
CRDT- 2007/06/20 09:00
PHST- 2007/06/20 09:00 [pubmed]
PHST- 2007/08/28 09:00 [medline]
PHST- 2007/06/20 09:00 [entrez]
AID - 10.1099/jmm.0.47050-0 [doi]
PST - ppublish
SO  - J Med Microbiol. 2007 Jul;56(Pt 7):896-906. doi: 10.1099/jmm.0.47050-0.