Effect On IL-8 And TNF-α Release, Expression Of NF-κB And Activity Of HDAC In Alveolar Macrophages (AM) From COPD

Objective: To investigate the effects of individual and combinated administration of dexamethasone, theophylline, and N-acetyleysteine (NAC) on IL-8 and TNF-α release , expression of nuclear factor kappaB (NF- κB) and activity of histone deacetylace(HDAC) in Alveolar macrophages(AMs) from COPD patients.Methods: AM isolated and purified from normal subjects, healthy smokers, and COPD patients were randomly divided into five groups The LPS stimulation group(LPS stimulation), the theophylline group (LPS stimulation+Theo), the dexamethasone group ((LPS stimulation+Dex), the NAC group((LPS stimulation+ NAC) and the combination group with dexamethasone, theophylline and NAC ((LPS stimulation+Dex +Theo+ NAQ.The IL-8 and TNF-α concentrations were determined by sandwich ELISA. The expression of NF-κB in AM was observed by immunohistochemistry technique. HDAC activity was measured in protein extracts from AM and expressed according to protein content.Results: Compared with normal ,the secretion of IL-8 and TNF-α was increased significantly in AM from smokers and COPD patients after LPS stimulation (P<0.01or0.05); Dexamethasone and NAC can reduce IL-8 and TNF-α release in AM from COPD patients and smokers (P<0.01); Combination group has more effect on inhibiting the secretion of IL-8 and TNF-α (P<0.001) .Compared with normal group, the expression of NF-κB was increased significantly in AM from smokers and COPD patients after LPS stimulation (P< 0.05 ). the expression of NF-κB was less in groups of drug settled than in LPS stimulating group(P<0.05),and decreased further in combination group(P<0.01).HDAC activity was significantly reduced in AM from COPD patients and smokers compared with normal subjects after LPS stimulation(P<0.05).Theophylline and NAC can increase HDAC activity in AM from COPD patients and smokers (P<0.01), while combination groups can increase more (P<0.01); .DEX has no effect on the activity of HDAC.Conclusion: The individual and combinated administration of low-doses theophylline, dexamethasone, and N-acetyleysteine can reduce the release of IL-8 and TNF-α, inhibit the expression of NF-κB; Low-doses theophylline and N-acetyleysteine can improve the activity of HDAC2; Combinated administration has better effect than individual in the treatmeant of COPD.