PMID- 22522044
OWN - NLM
STAT- MEDLINE
DCOM- 20120912
LR  - 20211021
IS  - 1096-1208 (Electronic)
IS  - 0882-4010 (Print)
IS  - 0882-4010 (Linking)
VI  - 53
IP  - 1
DP  - 2012 Jul
TI  - Regulation of inducible heme oxygenase and cyclooxygenase isozymes in a mouse 
      model of spotted fever group rickettsiosis.
PG  - 28-36
LID - 10.1016/j.micpath.2012.03.010 [doi]
AB  - Vascular endothelial cells (ECs) lining the blood vessels are the preferred 
      primary targets of pathogenic Rickettsia species in the host. In response to 
      oxidative stress triggered by infection, ECs launch defense mechanisms such as 
      expression of heme oxygenase-1 (HO-1). Previous evidence from an established 
      animal model of Rocky Mountain spotted fever also suggests selective modulation 
      of anti-oxidant enzyme activities in the target host tissues. In this study, we 
      have examined the expression profiles of HO-1 and COX-2 in different tissues 
      during Rickettsia conorii infection of susceptible C3H/HeN mice. RNA 
      hybridization with murine HO-1 and COX-2-specific complementary DNA probes 
      revealed increased HO-1 expression in the liver and brain of mice infected with 
      three different doses of R. conorii ranging from 2.25x10(3) to 2.25x10(5) pfu, 
      relatively non-remarkable changes in the lungs, and a trend for down-regulation 
      in the spleen. The most prominent HO-1 response was evident in the liver with 
       approximately 4-fold increase on day 4 post-infection, followed by a decline on day 7. HO-1 
      expression in the brain, however, peaked with significantly higher levels on day 
      7. Following infection with both sub-lethal as well as lethal doses of infection, 
      the transcript encoding COX-2 also displayed a pattern of increased expression in 
      the liver and brain. Although immunohistochemical staining revealed increased 
      abundance of HO-1 protein in the liver of infected mice, adjoining serial 
      sections did not exhibit positive staining for COX-2 in infected tissues. The 
      levels of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte-derived 
      cytokine (KC) were significantly higher in the sera of infected mice and 
      corresponded with the onset and severity of the disease. Treatment of infected 
      animals with anti-oxidants alpha-lipoic acid and N-acetylcysteine and HO inhibitor 
      stannous protoporphyrin (SnPPIX) showed only selective beneficial effects on HO-1 
      and COX-2 expression in the liver and spleen and serum levels of KC and MCP-1. R. 
      conorii infection of susceptible mice, therefore, results in selective regulation 
      of the expression of HO-1 and COX-2 in a manner dependent on the target host 
      tissue's cellular environment and the propensity of infection with rickettsiae.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Rydkina, Elena
AU  - Rydkina E
AD  - Department of Microbiology and Immunology, University of Rochester School of 
      Medicine and Dentistry, Rochester, New York, USA.
FAU - Turpin, Loel C
AU  - Turpin LC
FAU - Sahni, Abha
AU  - Sahni A
FAU - Sahni, Sanjeev K
AU  - Sahni SK
LA  - eng
GR  - R01 AI067613/AI/NIAID NIH HHS/United States
GR  - R21 AI076697/AI/NIAID NIH HHS/United States
GR  - AI067613/AI/NIAID NIH HHS/United States
GR  - AI076697/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120410
PL  - England
TA  - Microb Pathog
JT  - Microbial pathogenesis
JID - 8606191
RN  - 0 (Isoenzymes)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Boutonneuse Fever/*pathology
MH  - Brain/enzymology/pathology
MH  - Cyclooxygenase 2/*metabolism
MH  - Disease Models, Animal
MH  - *Gene Expression Regulation
MH  - Heme Oxygenase-1/*metabolism
MH  - Isoenzymes/metabolism
MH  - Liver/enzymology/pathology
MH  - Lung/enzymology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Rickettsia conorii/*pathogenicity
MH  - Spleen/enzymology/pathology
PMC - PMC3923379
MID - NIHMS369807
EDAT- 2012/04/24 06:00
MHDA- 2012/09/13 06:00
PMCR- 2014/02/13
CRDT- 2012/04/24 06:00
PHST- 2011/03/28 00:00 [received]
PHST- 2012/03/16 00:00 [revised]
PHST- 2012/03/26 00:00 [accepted]
PHST- 2012/04/24 06:00 [entrez]
PHST- 2012/04/24 06:00 [pubmed]
PHST- 2012/09/13 06:00 [medline]
PHST- 2014/02/13 00:00 [pmc-release]
AID - S0882-4010(12)00076-9 [pii]
AID - 10.1016/j.micpath.2012.03.010 [doi]
PST - ppublish
SO  - Microb Pathog. 2012 Jul;53(1):28-36. doi: 10.1016/j.micpath.2012.03.010. Epub 
      2012 Apr 10.