Effect of corticosteroids and neuropeptides on the expression of defensins in bovine tracheal epithelial cells.
Susceptibility to bacterial pneumonia in cattle is enhanced by stressors such as transportation, weaning, and commingling, which trigger a physiologic stress response resulting in elevated levels of endogenous corticosteroids and catecholamines. To determine the effect of neuroendocrine mediators on the expression of innate defense peptides in the lung, bovine tracheal epithelial cells were exposed to dexamethasone, catecholamines, acetylcholine, or substance P, and then beta-defensin expression was quantified using real-time reverse transcription-PCR. Basal expression of tracheal antimicrobial peptide (TAP) mRNA was not affected by any of the mediators tested. However, induction of TAP expression by lipopolysaccharide was significantly inhibited by pretreatment with dexamethasone. Bronchial biopsy specimens from dexamethasone-treated calves had significantly lower expression of TAP and lingual antimicrobial peptide (LAP) mRNA than saline-treated controls following 48 h of treatment. Lipopolysaccharide-elicited neutrophil recruitment was enhanced in the lungs of dexamethasone-treated calves compared to saline-treated controls. These findings indicate that modulation of epithelial antimicrobial peptide expression is one mechanism through which corticosteroids and stress may impair innate pulmonary defenses.
Mitchell
Gordon B
GB
Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada. gmitchel@uoguelph.ca
Al-Haddawi
Muthafar H
MH
Clark
Mary Ellen
ME
Beveridge
Jennifer D
JD
Caswell
Jeff L
JL
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D009479:Neuropeptides / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D023083:beta-Defensins; C107762:tapasin; D003907:Dexamethasone