Induction of Tachykinin production in airway epithelia in response to viral infection

Abstract

Background: The tachykinins are implicated in neurogenic inflammation and the neuropeptide substance P in the particular has been shown to be a proinflammatory mediator. A role for the tachykinins in host response to long challenge has been previously demonstrated but has been focused predominantly on the release of the tachykinins from nerves innervating the long. We have previously demonstrated the most dramatic phenotype described for the substance P encoding gene preprotachykinin-A (PPT-A) to date in controlling the host immune response to the gammaherpesvirus 68 in the lung. Methodolgy/Principal Findings: In this study we have utilised transgenic mice engineered to co-ordinately express the beta-galactosidase marker gene along with PPT-A to facilitate the tracking of PPT-A expression. Using a combination of these mice and conventional immunohistology we now demonstrate that PPT-A gene expression and substance P peptide are induced in cells of the respiratory trace including tracheal, bronchiolar and alveolar epithelial cells and macrophages afyter viral infection. This induction was observed 24th post infection, prior to observable inflammation and the expression of pro-inflammatory chemokines in this model. Induced expression of the PPT-A gene and peptide persisted in the lower respiratory tract through day 7 post infection. Conclusions/Significance: Non-neuronal PPT-A expression after infection may have important clinical implications for the progression or management of lung disease or infection aside from the well characterised later involvement of the tachykinins during the inflammatory response. © 2008 Stewart et al.