Expression of CREB-binding protein and peroxisome proliferator-activated receptor gamma during formoterol or formoterol and corticosteroid therapy of chronic obstructive pulmonary disease.
We assessed the effect of therapy on nuclear signaling related to inflammatory processes in sputum cells of patients with chronic obstructive pulmonary disease (COPD). Patients were treated with formoterol (F) or formoterol plus budesonide (F/ICS) b.i.d. for 4 weeks, their sputum cells were isolated and subjected to RNA extraction or lysis, followed by differential centrifugation. Signaling protein levels were assessed by Western blots, their specific mRNAs were quantified using qRTPCR, while 8-isoprostane levels were examined using enzyme immunoassay kit. Cytosolic 8-isoprostane levels and nuclear glucocorticoid receptor expression (protein and mRNA) were not significantly different in both groups, while nuclear cAMP response element binding protein (CREB; protein and mRNA) and peroxisome proliferator-activated receptor gamma (PPARgamma protein and mRNA) were significantly higher in cells from F/ICS-treated patients. CREB-binding protein (CBP; protein and mRNA) levels were significantly lower in F/ICS patients. These changes indicate increased anti-inflammatory signaling in F/ICS-treated patients and seem to be beneficial.
Holownia
A
A
Department of Clinical Pharmacology, Bialystok Medical University, Bialystok, Poland. holow_sinai@hotmail.com
Mroz
R M
RM
Noparlik
J
J
Chyczewska
E
E
Braszko
J J
JJ
D015153:Blotting, Western; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D050882:CREB-Binding Protein / Q000096:biosynthesis*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D004983:Ethanolamines / Q000627:therapeutic use*; D005541:Forced Expiratory Volume / Q000502:physiology; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000096:biosynthesis*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013183:Sputum / Q000166:cytology
D001993:Bronchodilator Agents; D004983:Ethanolamines; D005938:Glucocorticoids; D047495:PPAR gamma; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D050882:CREB-Binding Protein; D000068759:Formoterol Fumarate