Source: Annual Congress 2002 - Cell biology and genetics of COPD and emphysema
Disease area: Airway diseases

Abstract

Cigarette-smoking is the main risk factor for developing COPD. The inflammatory cytokines IL-8 and GM-CSF are important for regulation and activation of neutrophils, T-lymphocytes, which are implicated in the pathogenesis of COPD.It is well known that in smokers (S)and COPD there is a higher expression of IL-8 in sputum, but little is known about smoking-induced regulation and cell signaling pathways of GM-CSF expression compared to IL-8.In this study we investigated the basal and IL-1β-induced IL-8 and GM-CSF expression in human peripheral blood monocytes (PBM). We studied the involvement of mitogen-activated protein-kinases (p38MAPK, MKK-1)and histone deacetylase HDAC)which is associated with gene silencing or transcriptional repression in this process and compared non-smokers (NS), S, and COPD.
There is a constitutive expression in basal IL-8 in NS, S and COPD (p>0.05)in contrast to GM-CSF. IL-1β (10 ng/ml) induced a significant increase in IL-8 and GM-CSF release with highest levels in S compared to NS and COPD (p<0.05). PD 098059, an inhibitor of MKK-1, decreased IL-1β-induced IL-8 expression by ~ 30 % (p<0.05, n=8) without differences between NS, S, COPD. In contrast, SB 203580, an inhibitor of the p38MAPK, decreased the expression of IL-8 by ~ 40 % in NS and COPD but ~70 % in S (p<0.05)and could reversed by 30 % in the presence of TSA, an inhibitor of HDAC (p<0.05). In comparison to that there was a differencial decrease in GM-CSF generation in the presence of PD 098059 and SB 203580 in NS (60 % and 80 %, p<0.05), COPD (57 % and 55 %, p<0.05)and S (75 % and 95 %, p<0.05).
We conclude that the IL-1β-induced expression of IL-8 and GM-CSF in PBM are increased in S compared to NS and COPD. There is a differential modulation of IL-8 and GM-CSF release by p38MAPK and MKK-1 in S compared to NS and COPD.

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M. D. Heimann, S. Nadolny, A. Schardey, A. Koch (Cologne, Germany). Differential modification in the generation of IL-8 and GM-CSF by p38MAPK, MKK-1 and histone deacetylase activity in IL-1[β]-stimulated human monocytes from non-smokers, smokers and patients with COPD. Eur Respir J 2002; 20: Suppl. 38, 633

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