Induction of tachykinin production in airway epithelia in response to viral infection.
BACKGROUND
The tachykinins are implicated in neurogenic inflammation and the neuropeptide substance P in particular has been shown to be a proinflammatory mediator. A role for the tachykinins in host response to lung challenge has been previously demonstrated but has been focused predominantly on the release of the tachykinins from nerves innervating the lung. 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 murine gammaherpesvirus 68, in the lung.


RESULTS
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 tract including tracheal, bronchiolar and alveolar epithelial cells and macrophages after viral infection. This induction was observed 24h 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
Non-neuronal PPT-A expression early 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.
Stewart
James P
JP
Department of Medical Microbiology, The University of Liverpool, Liverpool, United Kingdom. j.p.stewart@liv.ac.uk
Kipar
Anja
A
Cox
Helen
H
Payne
Catherine
C
Vasiliou
Sylvia
S
Quinn
John P
JP
D000818:Animals; D004848:Epithelium / Q000378:metabolism* / Q000821:virology; D018142:Gammaherpesvirinae / Q000235:genetics* / Q000254:growth & development; D006566:Herpesviridae Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D010446:Peptide Fragments; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D001616:beta-Galactosidase