Cyclooxygenase-2 is up-regulated in lung parenchyma of chronic obstructive pulmonary disease and down-regulated in idiopathic pulmonary fibrosis.
OBJECTIVE
In vitro studies have suggested that fibroblasts from idiopathic pulmonary fibrosis (IPF) may have an impaired induction of cyclooxygenase (Cox)-2. We have investigated Cox-1 and Cox-2 expression in lung tissue from IPF.


METHODS
Cox-1 and Cox-2 expression were determined using RT-competitive PCR and immunohistochemistry in pulmonary biopsies from IPF (n = 22), chronic obstructive pulmonary disease (COPD) (n = 13), and lung tissue from subjects undergoing pleurodesis for spontaneous pneumothorax (control group, n = 17).


RESULTS
Immunohistochemical analysis showed that the score of Cox-2 positive cells was higher in COPD (1 +/- 0) with respect to fibrosis (0.37 +/- 0.1, p < 0.05) and controls (0.57 +/- 0.2). There were no differences between fibrosis and controls in Cox-2 positive cells. The expression of Cox-2 mRNA was significantly higher in COPD (3.26 +/- 0.72 x 10(6) molecules cDNA/microg total RNA) in comparison to IPF (0.57 +/- 0.17) and controls (0.54 +/- 0.16) (p < 0.001). After IL-1beta stimulation (1-10 ng/ml) Cox-2 mRNA basal expression increased significantly in controls (from 35 +/- 12 to 94 +/- 4 x10(6) molecules cDNA/microg total RNA, p < 0.01) and in COPD (from 38 +/- 8 to 92 +/- 3, p < 0.01). In contrast, no significant changes in Cox-2 mRNA expression were found in IPF (from 30 +/- 12 to 43 +/- 16).


CONCLUSIONS
Our results suggest that differences in Cox-2 expression may play a role in the regulation of inflammatory responses in lung diseases. Excessive activity is associated with the development of chronic obstructive lung disease, while a limited activation following pro-inflammatory stimulation might contribute to fibrogenic responses.
Xaubet
Antoni
A
Servei de Pneumologia i Allèrgia Respiratòria, Institut Clinic de Pneumologia i Cirurgia Toràcica, Barcelona, Spain.
Roca-Ferrer
Jordi
J
Pujols
Laura
L
Ramírez
Josep
J
Mullol
Joaquim
J
Marin-Arguedas
Alejandra
A
Torrego
Alfons
A
Gimferrer
Josep Maria
JM
Picado
Cesar
C
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D051546:Cyclooxygenase 2; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007527:Isoenzymes / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases