Specimens of lung tissue obtained from patients with increasing clinical stages of COPD had graded reductions in HDAC activity and increases in interleukin-8 messenger RNA (mRNA) and histone-4 acetylation at the interleukin-8 promoter.
Although IL-8 plays an important role in the chemotaxis of inflammatory cells, the polymorphisms investigated here do not seem to be involved in the genetic predisposition to COPD.
The inflammatory chemokines interleukin-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1, are reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A.
After 18 h of cell culture the basal release of MMP-9 was 2.5-fold, p < 0.02 greater, whereas IL-8 was 1.8-fold (p < 0.01) lower from COPD patient monocytes than from controls.
In comparison with the nonrespiratory surgical procedure and S-COPD groups, neutrophilia and gene expression for epithelial-derived neutrophil attractant-78 (CXCL5), interleukin-8 (CXCL8), CXCR1, and CXCR2 were each upregulated in the E-COPD group (p < 0.01); compared with the S-COPD group, by 97-, 6-, 6-, 3-, and 7-fold, respectively (p < 0.01).
In subjects with COPD, semi-quantitative analysis revealed 1.5-fold higher levels of MCP-1 mRNA and IL-8 mRNA and protein in bronchiolar epithelium (p<0.01) and 1.4-fold higher levels of CCR2 in macrophages (p=0.014) than in subjects without COPD.