Regulation of inducible heme oxygenase and cyclooxygenase isozymes in a mouse model of spotted fever group rickettsiosis

Elena Rydkina, Loel C. Turpin, Abha Sahni, Sanjeev K. Sahni

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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 2.25×10 3 to 2.25×10 5pfu, 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 ~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 α-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.

Original languageEnglish (US)
Pages (from-to)28-36
Number of pages9
JournalMicrobial Pathogenesis
Volume53
Issue number1
DOIs
StatePublished - Jul 1 2012

    Fingerprint

Keywords

  • Chemokines
  • Cyclooxygenase
  • Endothelial cells
  • Heme oxygenase
  • Mouse model of infection
  • Rickettsia conorii
  • Rocky mountain spotted fever

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this