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Induction of B7-H1 and B7-DC expression on airway epithelial cells by the Toll-like receptor 3 agonist double-stranded RNA and human rhinovirus infection: In vivo and in vitro studies

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Background

T-cell infiltration of the epithelium is a key feature of chronic rhinosinusitis and asthma. Viral infections are an important cause of disease exacerbations. We have found virus-induced expression of T cell–interacting ligands, B7 homolog costimulatory molecules, on airway epithelium.

Objective

We tested the ability of human rhinovirus (HRV) 16 and double-stranded RNA (dsRNA) to alter the expression of B7 homologs on human airway epithelial cells.

Methods

BEAS2B and primary human airway epithelial cells were exposed in vitro to dsRNA (25 μg/mL) or HRV-16, and then expression of cell-surface protein and mRNA for B7 homologs was assessed by means of flow cytometry and real-time PCR, respectively. Additionally, human subjects were infected with HRV-16 in vivo, and mRNA for B7 homologs was assessed by means of real-time PCR in fresh nasal epithelial cell scrapings obtained before and daily up to 4 days after infection.

Results

dsRNA exposure of BEAS2B and human primary bronchial epithelial cells resulted in increased levels of cell-surface and mRNA expression of B7-H1 and B7-DC but not B7-H2 or B7-H3. Exposure of primary cells to HRV-16 resulted in induction of cell-surface expression of B7-H1 and B7-DC. Pretreatment with fluticasone propionate failed to suppress the induction of B7-H1 and B7-DC. Nasal scrapings taken at the time of peak symptom scores (3 days) after infection of 6 human subjects with HRV-16 displayed selective induction of levels of mRNA for B7-H1 and B7-DC.

Conclusion

These data show that HRV-16 infection or exposure to dsRNA induces epithelial B7-H1 and B7-DC.

Section snippets

Rationale

To test the hypothesis that mucosal inflammation triggered by viral dsRNA might regulate B7 homolog expression, we examined the effect of synthetic dsRNA and anti-inflammatory glucocorticoid on B7 homolog expression in the immortalized BEAS2B airway epithelial cell line. Next we examined the ability of dsRNA to induce B7 homolog expression in cultured human primary bronchial epithelial cells (PBECs). Because HRV-16 is known to be a key trigger of exacerbations of CRS and asthma, we examined

Effect of dsRNA on B7 homolog expression in BEAS2B cells

The data in Fig 1 (upper panel) show that 24-hour exposure to dsRNA increased cell-surface expression of B7-H1 and B7-DC but not B7-H2 or B7-H3 in BEAS2B cells. mRNA analysis by means of real-time PCR supported these findings in that both B7-H1 and B7-DC mRNA levels were selectively induced in response to 24-hour exposure to dsRNA (Fig 1, lower panel). In contrast, dsRNA and fluticasone had little or no effect on levels of cell-surface expression and mRNA expression of B7-H2 and B7-H3. The

Discussion

Interactions between T cells and epithelial cells are thought to be important in the pathogenesis of asthma and CRS. Products of both TH1- and TH2-activated T cells are known to stimulate proinflammatory cytokine and chemokine production in epithelial cells. IL-4 and IL-13 secreted from TH2-activated T cells are known to stimulate signal transducer and activator of transcription 6–dependent secretion of eotaxin and other CC chemokines in epithelial cells.27, 28 Additionally, IL-1 and TNF-α are

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    Supported by National Institutes of Health grants (AI57400, M01-RR-02719, HL068546, and HL078860) and Flight Attendant Medical Research Institute.

    Disclosure of potential conflict of interest: D. Proud has received research support from AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

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