[Effect of phosphodiesterase inhibitor on expression of IL-8 mRNA in peripheral blood mononuclear cells from COPD patients].
OBJECTIVE
To explore the inhibitory mechanism of phosphodiesterase(PDE) inhibitor on expression of IL-8 mRNA in peripheral blood mononuclear cells (PBMCs) from chronic obstructive pulmonary disease(COPD) patients.


METHODS
PBMCs isolated from 20 COPD patients and 15 healthy subjects were co-cultured with non-selective inhibitor theophylline or PDE type IV inhibitor Rolipram. The expression of IL-8 mRNA was assayed by RT-PCR. The expression of NF-kappaB was determined by immunocytochemical staining. The content of I-kappaB protein was detected by Western blot.


RESULTS
The expression of IL-8 mRNA was elevated and the percentage of NF-kappaB nucleus positive cells was higher in COPD patients than in normal controls(P<0.01), while the expression of I-kappaB was lower in COPD patients (P<0.01). Theophylline of 1 mmol/L caused a decrease in the percentage of NF-kappaB nucleus positive cells (P<0.05). The expression of IL-8 mRNA and I-kappaB were not affected by theophylline at the dose of 100 micromol/L or 1 mmol/L. Rolipram inhibited the expression of IL-8 mRNA and the activation of NF-kappaB(P<0.05).


CONCLUSIONS
The results indicated that IL-8 mRNA may play a pathogenic role in the development of COPD and that selective PDE type IV inhibitor Rolipram inhibit the expression of IL-8 mRNA via NF-kappaB.
Yang
Dan-lei
DL
Department of Respiratory Diseases, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China. yangdanlei@126.com
Xu
Yong-jian
YJ
Zhang
Zhen-xiang
ZX
Li
Chao-qian
CQ
Ni
Wang
W
D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger