Pre-protachykinin-A mRNA is increased in the airway epithelium of smokers with chronic bronchitis.
OBJECTIVE
Tachykinins are neuropeptides present in sensory nerves in the lung. Aside from their role as neurotransmitters, these peptides exert pro-inflammatory and protective effects in the airways. Although tachykinins may be released from sensory nerves, there is increasing evidence that they are also produced by non-neuronal cells. The net effect of tachykinins will likely result from relative changes in the levels of tachykinins, tachykinin receptors and tachykinin degrading enzymes. We investigated whether tachykinins might be produced locally in human airway epithelium in vivo, and whether mRNA levels for either tachykinins, their receptors, or for the tachykinin degrading enzyme neutral endopeptidase (NEP) were altered in subjects with chronic bronchitis compared to normals.


METHODS
We used reverse transcription polymerase chain reaction analysis of brush biopsy samples to detect mRNAs of interest. We then developed a semi-quantitative approach to compare subject groups.


RESULTS
We detected a signal for preprotachykinin A (PPT-A) mRNA as well as for tachykinin receptors and NEP in patients with airways disease and normal subjects. We found a relative 10-fold increase in PPT-A mRNA in smokers with chronic bronchitis, along with similar increases in mRNA for the inflammatory markers intercellular adhesion molecule-1 and interleukin-8. In contrast, NEP and NK1 tachykinin receptor mRNA levels were not different between the groups.


CONCLUSIONS
These findings imply that up-regulation of tachykinin production by cells present in the airway epithelium contributes to the pathophysiology of chronic bronchitis.
Reynolds
P N
PN
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia. Paul.Reynolds@ccc.uab.edu
Scicchitano
R
R
Holmes
M D
MD
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D001980:Bronchi / Q000378:metabolism*; D001991:Bronchitis / Q000209:etiology / Q000503:physiopathology*; D001999:Bronchoscopy; D002908:Chronic Disease; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology*; D015320:Tachykinins / Q000378:metabolism*
D000199:Actins; D016209:Interleukin-8; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; C054618:protachykinin; D018799:Intercellular Adhesion Molecule-1; D015260:Neprilysin