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Rhinoviruses induce interleukin-8 mRNA and protein production in human monocytes
S L Johnston1, A Papi, M M Monick
1Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa College of Medicine, and VA Medical Center, Iowa City, USA.
Abstract:
Rhinoviruses are important upper respiratory pathogens that are strongly associated with asthma exacerbations. However, the inflammatory response to rhinovirus infection is poorly understood. Interleukin (IL)-8 has been implicated in the pathogenesis of respiratory viral infections and asthma. Rhinovirus-induced IL-8 release and mRNA induction were examined in peripheral blood mononuclear cells (PBMC). Rhinoviruses induced IL-8 release for up to 7 days after inoculation onto PBMC. This was associated with an increase in IL-8 mRNA expression that peaked 48 h after exposure to the virus. IL-8 protein production was reduced by UV inactivation of the virus and abolished by preventing virus-receptor binding. Although rhinovirus replication was not demonstrated in PBMC, low-grade productive infection was shown in the human monocyte cell line THP-1. Rhinovirus induction of IL-8 in monocytes or airway macrophages may be important in the pathogenesis of rhinovirus-induced asthma exacerbation.
Insights
Rhinoviruses trigger significant interleukin-8 (IL-8) release and gene expression in immune cells, contributing to asthma exacerbations. This response is linked to viral presence and receptor binding, highlighting IL-8
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Rhinoviruses are key triggers of asthma exacerbations.
- The precise inflammatory mechanisms underlying rhinovirus-induced asthma flares remain unclear.
- Interleukin-8 (IL-8) is a cytokine implicated in respiratory viral infections and asthma pathogenesis.
Purpose of the Study:
- To investigate rhinovirus-induced interleukin-8 (IL-8) release and gene expression in peripheral blood mononuclear cells (PBMC).
- To explore the role of viral replication and interaction in IL-8 production.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) were inoculated with rhinoviruses.
- IL-8 protein levels and mRNA expression were measured over time.
- Virus inactivation (UV) and receptor-blocking were used to assess IL-8 induction mechanisms.
- Rhinovirus replication was assessed in PBMC and the THP-1 monocyte cell line.
Main Results:
- Rhinoviruses induced sustained IL-8 release from PBMC for up to 7 days.
- IL-8 mRNA expression peaked at 48 hours post-exposure.
- UV inactivation reduced IL-8 production, while blocking virus-receptor interaction abolished it.
- Low-grade rhinovirus replication was observed in THP-1 cells, but not significantly in PBMC.
Conclusions:
- Rhinovirus infection stimulates significant IL-8 production in immune cells.
- IL-8 induction is dependent on viral viability and interaction with cellular receptors.
- Rhinovirus-induced IL-8 in monocytes and macrophages may play a crucial role in asthma exacerbations.