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Interleukin-1 is linked to the respiratory epithelial cytopathology of pertussis
L N Heiss1, S A Moser, E R Unanue
1Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Abstract:
Bordetella pertussis, the causative agent of whooping cough, releases a muramyl peptide known as tracheal cytotoxin (TCT) that is responsible for destruction of ciliated epithelial cells lining the large airways. In vitro, TCT has been shown to cause this specific pathology in human or hamster respiratory epithelium and to inhibit the proliferation of cultured hamster trachea epithelial cells. The diverse biological actions of muramyl peptides, including adjuvanticity, somnogenicity, and pyrogenicity, have been correlated with the production and release of the inflammatory mediator interleukin-1 (IL-1). Consistent with its ability to reproduce other muramyl peptide actions, recombinant IL-1 caused TCT-like damage to the respiratory epithelium. In the nanogram-per-milliliter range, exogenous IL-1 inhibited DNA synthesis in hamster trachea epithelial cells and reproduced the pathology of TCT in hamster tracheal organ culture. Tumor necrosis factor alpha and IL-6, cytokines also associated with inflammation, were unable to reproduce TCT cytopathology. Furthermore, exposure of respiratory epithelial cells to TCT stimulated production of cell-associated IL-1 alpha, which could be detected within 2 h of TCT treatment. In contrast, there was no evidence of TCT-triggered release of IL-1. Previous studies have suggested that intracellular IL-1 alpha, as well as exogenous IL-1 alpha and IL-1 beta, can inhibit cell proliferation. Our results therefore implicate IL-1 alpha, produced by epithelial cells in response to TCT, as a potential intracellular mediator of the primary respiratory cytopathology of pertussis.
Insights
Bordetella pertussis releases tracheal cytotoxin (TCT), damaging airway cells. Interleukin-1 (IL-1) produced by these cells mediates this damage, implicating it in whooping cough pathology.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Bordetella pertussis causes whooping cough by releasing tracheal cytotoxin (TCT).
- TCT destroys ciliated epithelial cells in the respiratory tract.
- Muramyl peptides, like TCT, are linked to inflammatory mediators such as interleukin-1 (IL-1).
Purpose of the Study:
- To investigate the role of IL-1 in TCT-induced respiratory epithelial damage.
- To determine if IL-1 mediates the cytopathology caused by TCT.
- To explore the cellular response of respiratory epithelium to TCT exposure.
Main Methods:
- In vitro studies using human and hamster respiratory epithelium.
- Organ culture of hamster trachea.
- Assessing DNA synthesis and cell proliferation.
- Measuring cytokine production (IL-1 alpha, IL-6, TNF-alpha).
Main Results:
- Recombinant IL-1 mimicked TCT-induced damage to respiratory epithelium.
- Exogenous IL-1 inhibited DNA synthesis in hamster trachea epithelial cells.
- TCT exposure stimulated the production of cell-associated IL-1 alpha within 2 hours.
- Tumor necrosis factor alpha and IL-6 did not reproduce TCT cytopathology.
Conclusions:
- IL-1, specifically IL-1 alpha produced intracellularly by epithelial cells, is implicated as a mediator of TCT-induced respiratory damage.
- This IL-1 alpha production is a key factor in the primary respiratory cytopathology of pertussis.
- The findings highlight a crucial mechanism in whooping cough pathogenesis.