Aim: 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).
Conclusion: 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.