Methods: We used C57BL/6 mice and BRP-39 null mice. Mice were inoculated with live A2-strain RSV and control PBS. Methacholine challenge test to measure airway resistance worked on day 5 after inoculation. And bronchoalveolar lavage fluid (BALF) samples were obtained and lung specimens were also harvested on days 5 after inoculation to assess lung inflammation, cytokine expression and BRP-39 production. BRP-39 expression was evaluated by ELISA. RSV loads were assessed by culture and real-time polymerase chain reaction (PCR). Histological evaluations of H&E and PAS staining were used to evaluate inflammation and tissue remodeling.
Results: Level of BRP-39 in BALF was significantly increased in wild-type (WT) mice after RSV infection, but not observed in BRP-39 null mice. Inflammatory changes induced by RSV infection were less in BRP-39-/- mice rather than WT mice. In WT mice, RSV infection caused loss of body weight and significant increase of total cells, macrophages and neutrophils in BALF. And exaggerated AHR was also noted in WT mice after RSV infection. But, BRP-39-/- mice showed decreased responses in each of these parameters. Between RSV infection groups, histological tissue inflammation was also decreased in BRP-39 -/-mice.
Conclusions: The role of early-onset wheezing with respiratory viral infections in childhood asthma inception has received attention. RSV has known as a significant risk factor for asthma that extends into adolescence and adults and its mechanism is still under investigation. In this study, expression of BRP-39 increased by RSV infection in mice. And inflammatory changes and AHR induced by RSV were decreased in BRP-39 null mice. These findings suggest Chi3L1 could contribute to airway inflammation induced by RSV infection in mice. Furthermore, Chi3L1 might be considered as a therapeutic target against viral wheezing or virus-induced asthma.