Modulation of expression of B7 homologs by human rhinovirus and double-stranded RNA in airway epithelial cells in vitro and in vivo

Abstract

Rationale Since respiratory RNA viruses are an important cause of exacerbations of sinusitis and asthma, we tested the ability of human rhinovirus-16 (HRV-16) and the toll-like receptor type 3 (TLR3) agonist, dsRNA, to alter expression of B7 homolog costimulatory molecules in human airway epithelial cells. Methods BEAS2B human airway epithelial cells were cultured to confluence, exposed to dsRNA (25 μg/ml), and then expression of mRNA and cell-surface protein for B7 homologs was assessed by real-time PCR and flow cytometry, respectively. Additionally, human subjects were infected with HRV-16 in vivo, and mRNA for B7-homologs was assessed by real-time PCR in fresh nasal epithelial cell scrapings obtained before and daily up to 4 days. Results Exposure of BEAS2B cells to dsRNA for 24 hours resulted in an increase in cell-surface and mRNA expression of B7-H1 (approx. 2 and 3 fold, respectively) and B7-DC (approx. 2.5 and 3.5 fold), but not B7-H2 or B7-H3 (p<0.05, n=3). Nasal scrapings taken at the time of peak symptom scores (4 days) after infection of 6 human subjects with HRV-16 had increased levels of mRNA for B7-H1 (8.5 ± 2.5 fold, p<0.03) and B7-DC (3.2 ± 1.1 fold, p<0.07), but no apparent increase in mRNA for B7-H2 and B7-H3. In vitro studies with HRV-16 are underway to determine whether direct induction of B7 homologs can occur in infected epithelial cells. Conclusion Increased expression of the B7 homologs B7-H1 and B7-DC by exposure of epithelial cells to the TLR3 agonist dsRNA or HRV-16 may influence the development of adaptive immune responses in the airways.