Human respiratory epithelial cells may act as antigen-presenting cells during respiratory viral infections. In addition to major histocompatibility complex (MHC) molecules, antigen presentation requires participation of costimulatory molecules. Here the authors investigated class I and class II antigens and B7-1 and B7-2 costimulatory molecule expression in human A549 pulmonary epithelial cells and primary bronchial epithelial cells (HBECs) at baseline and after rhinovirus infection. Constitutive expression of MHC class I and B7-1 molecules was observed on both cell types. MHC class I molecules were up-regulated by rhinovirus infection, while B7-1 was up-regulated only on A549 cells. B7-2 molecules were constitutively expressed at a low level and were up-regulated by rhinovirus only on HBECs. Rhinovirus induction of antigen-presenting molecule expression on A549 cells was accompanied by cellular activation in terms of induction of release of the chemokines RANTES and Groalpha. These data show that respiratory epithelium expresses full antigen-presentation machinery and that rhinovirus infection up-regulates this expression.

Rhinoviruses are associated with the majority of asthma exacerbations. To date, the pathogenesis of virus-induced asthma exacerbations is still unclear, and no safe effective therapy is available. Intercellular adhesion molecule-1 (ICAM-1) has a central role in inflammatory cell recruitment to the airways in asthma and is the receptor for 90% of rhinoviruses. We have previously shown that rhinovirus infection of lower airway epithelium induces ICAM-1 expression by a transcriptional mechanism that is critically nuclear factor-kappaB-dependent.|The purpose of this study was to investigate the effect of systemic (hydrocortisone [HC], dexamethasone [DM]) and topical (mometasone furoate [MF]) corticosteroids on rhinovirus-induced ICAM-1 up-regulation.|Cultured primary bronchial or transformed (A549) respiratory epithelial cells were pretreated with corticosteroids for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluated by flow cytometry. In A549 cells ICAM-1 messenger RNA was evaluated by specific reverse transcription-PCR and promoter activation by chloramphenicol acetyltransferase assay.|We observed inhibition of rhinovirus-induced ICAM-1 up-regulation with corticosteroid pretreatment in both primary bronchial epithelial and A549 cells. In A549 cells systemic and topical corticosteroids demonstrated a dose-dependent inhibition with similar efficacy (inhibitory concentration 50% 10(-10) mol/L, 10(-11) mol/L, and 10(-11) mol/L for HC, DM, and MF respectively). MF also inhibited ICAM-1 messenger RNA induction by rhinovirus infection in a dose-dependent manner. MF completely inhibited rhinovirus-induced ICAM-1 promoter activation. HC, DM, and MF had no direct effect on rhinovirus infectivity and replication in cultured cells.|Corticosteroids decrease rhinovirus-induced ICAM-1 up-regulation in respiratory epithelial cells and modulate pretranscriptional mechanisms. This effect may be important for the therapeutic control of virus-induced asthma exacerbations.

Rhinoviruses (RVs) are the most common upper respiratory pathogens, inducing the majority of common colds worldwide. RV-related morbidity, although significant cumulatively, has been considered trivial for the individual patient. However, recent strong epidemiological associations of RVs with asthma exacerbations, including severe episodes requiring hospitalization, indicate that RV infections can result in serious disease. Current evidence supports the possibility that RVs infect the lower airways, inducing a local inflammatory response. Such evidence suggests that the role of RVs in other lower respiratory diseases, such as pneumonia, bronchitis, bronchiolitis and cystic fibrosis, should be re-examined with polymerase chain reaction-based methodologies, which are considerably more sensitive than traditional, cell culture-based techniques. The mechanisms through which RVs induce lower airway disease are studied to understand the relative contributions of the epithelial, neurogenic and immune components in the antiviral response, and to permit the design and implementation of specific treatments.

Rhinoviruses are the major cause of the common cold and a trigger of acute asthma exacerbations. Whether these exacerbations result from direct infection of the lower airway or from indirect mechanisms consequent on infection of the upper airway alone is currently unknown. Lower respiratory infection was investigated in vitro by exposing primary human bronchial epithelial cells to rhinoviruses and in vivo after experimental upper respiratory infection of human volunteers. Bronchial infection was confirmed by both approaches. Furthermore, rhinoviruses induced production of interleukin-6, -8, and -16 and RANTES and were cytotoxic to cultured respiratory epithelium. This evidence strongly supports a direct lower respiratory epithelial reaction as the initial event in the induction of rhinovirus-mediated asthma exacerbations. The frequency of infection and the nature of the inflammatory response observed are similar to those of the upper respiratory tract, suggesting that rhinovirus infections may be one of the most important causes of lower in addition to upper respiratory disease.