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Mycoplasma pneumoniae CARDS toxin exacerbates ovalbumin-induced asthma-like inflammation in BALB/c mice.

Abstract
Mycoplasma pneumoniae causes a range of airway and extrapulmonary pathologies in humans. Clinically, M. pneumoniae is associated with acute exacerbations of human asthma and a worsening of experimentally induced asthma in mice. Recently, we demonstrated that Community Acquired Respiratory Distress Syndrome (CARDS) toxin, an ADP-ribosylating and vacuolating toxin synthesized by M. pneumoniae, is sufficient to induce an asthma-like disease in BALB/cJ mice. To test the potential of CARDS toxin to exacerbate preexisting asthma, we examined inflammatory responses to recombinant CARDS toxin in an ovalbumin (OVA) murine model of asthma. Differences in pulmonary inflammatory responses between treatment groups were analyzed by histology, cell differentials and changes in cytokine and chemokine concentrations. Additionally, assessments of airway hyperreactivity were evaluated through direct pulmonary function measurements. Analysis of histology revealed exaggerated cellular inflammation with a strong eosinophilic component in the CARDS toxin-treated group. Heightened T-helper type-2 inflammatory responses were evidenced by increased expression of IL-4, IL-13, CCL17 and CCL22 corresponding with increased airway hyperreactivity in the CARDS toxin-treated mice. These data demonstrate that CARDS toxin can be a causal factor in the worsening of experimental allergic asthma, highlighting the potential importance of CARDS toxin in the etiology and exacerbation of human asthma.
AuthorsJorge L Medina, Jacqueline J Coalson, Edward G Brooks, Claude Jourdan Le Saux, Vicki T Winter, Adriana Chaparro, Molly F R Principe, Laura Solis, T R Kannan, Joel B Baseman, Peter H Dube
JournalPloS one (PLoS One) Vol. 9 Issue 7 Pg. e102613 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID25058417 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Proteins
  • Bacterial Toxins
  • CARDS toxin, Mycoplasma pneumoniae
  • Ccl17 protein, mouse
  • Ccl22 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL22
  • Interleukin-13
  • Recombinant Proteins
  • Interleukin-4
  • Ovalbumin
Topics
  • Animals
  • Asthma (chemically induced, immunology, pathology)
  • Bacterial Proteins (toxicity)
  • Bacterial Toxins (toxicity)
  • Bronchial Hyperreactivity (chemically induced, immunology, pathology)
  • Bronchoalveolar Lavage Fluid (chemistry, cytology)
  • Chemokine CCL17 (biosynthesis, immunology)
  • Chemokine CCL22 (biosynthesis, immunology)
  • Eosinophils (immunology, pathology)
  • Humans
  • Inflammation (chemically induced, immunology, pathology)
  • Interleukin-13 (biosynthesis, immunology)
  • Interleukin-4 (biosynthesis, immunology)
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin (administration & dosage)
  • Recombinant Proteins (toxicity)
  • Respiratory System (drug effects, immunology, pathology)
  • Th2 Cells (immunology, pathology)

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