LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells.
Our previous studies show that Bcl-2, a regulator of apoptosis, may be involved in the reduction of mucous cell metaplasia (MCM) during recovery from inflammatory responses. The present study was to determine whether neutrophilic inflammation mediates Bcl-2 expression in mucous cells. Rats were intratracheally instilled with 50-1000 microg of LPS. The number of neutrophils recovered by bronchoalveolar lavage (BAL) increased with the dose of LPS, and the percentage of Bcl-2-expressing cells increased with the numbers of neutrophils in the BAL. Depletion of neutrophils did not reduce MCM, but the percentage of Bcl-2-positive cells increased 1.8-fold in neutrophil-depleted compared with controls. Injection of rats with bezafibrate, an inducer of cytochrome P-450, doubled the number of neutrophils in the BAL, decreased MCM twofold compared with vehicle-injected controls, and reduced Bcl-2 expression. Bcl-2 mRNA levels decreased in a tracheal epithelial cell line treated with bezafibrate. These data demonstrate that Bcl-2 expression is independent of the number of neutrophils in the BAL and that bezafibrate may directly reduce Bcl-2 expression in epithelial cells.
Foster
Jennifer E
JE
Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
Gott
Katherine
K
Schuyler
Mark R
MR
Kozak
Wieslaw
W
Tesfaigzi
Yohannes
Y
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D019254:Genes, bcl-2 / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D008297:Male; D008679:Metaplasia; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D017931:DNA Primers; D000960:Hypolipidemic Agents; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D001629:Bezafibrate