TNF-Receptor Subtype Expression

For all correlations tested, inverse relationships between protein release and airway obstruction were found. With the exception of FEV₁/FVC (percentage predicted) vs GRO-a (p = 0.06, r = — 0.49), all correlations reached the level of significance (Table 2). Furthermore, no differences were seen with respect to the unstimulated protein release, and both cytokines responded nonsignificantly to IFN-y stimulation, which reflects the mRNA results as well.

Table 1—Increase in Stimulated Epithelial mRNA Expression Levels of IL-8 and GRO-a Relative to Unstimulated mRNA Levels*
 

	Basal	TNF-a	Fold Increase in TNF-a	IFN-y	Fold Increase in IFN-y
IL-8 mRNA
Smokers	1.0 (0.5-3.2)	4.6 (3.1-9.9)	4.7(1.8-14.1)	0.4 (0.1-1.3)	0.3 (0.1-0.9)
COPD	3.3 (0.2-19.1)	12.9 (5.4-36.9)t	5.7 (1.9-70.0)	1.9 (0.3-12.4)	0.9 (0.1-1.8)
GRO-a
mRNA Smokers	4.3 (0.9-8.9)	7.3 (3.8-11.2)	2.0 (0.7-9.1)	4.3 (0.8-6.5)	1.0 (0.2-2.0)
COPD	4.1 (0.9-12.3)	16.2 (8.1-81.8)t	4.3 (2.5-9.9)	5.7 (2.8-17.3)	1.8 (0.6-3.2)

*Data are presented as median (range). tp < 0.01 vs smokers without airway obstruction.

TNF-Receptor Subtype Expression

In addition to the TNF-a-induced cytokine responses, the expression levels of the TNF-receptor subtypes—p55 TNF-receptor subtype (TNF-R55) and p75 TNF-receptor subtype (TNF-R75)—were quantified at the steady-state mRNA level by means of light cycler measurements. As shown in Figure 3, both TNF receptors were detectable in PBECs. The expression levels of TNF-R55 compared to TNF-R75 were 5,670-fold and 4,730-fold higher in smokers without airflow limitation and patients with COPD, respectively. No significant differences in the expression levels between groups were detected for TNF-R55 (p = 0.8) nor for TNF-R75 (p = 0.6). Table 2 —Correlations Between TNF-a-Induced Protein Release of IL-8 or GRO-a in PBECs and Lung Function 

Parameters*

 

Variables	IL-8		GRO-a
	1 r Value	1 p Value	i r Value	l p Value
IL-8			0.72	< 0.01
FEV1, L	— 0.63	< 0.01	— 0.67	< 0.01
FEV1, % predicted	— 0.52	< 0.05	— 0.67	< 0.01
FEV1/FVC, %	— 0.67	< 0.01	— 0.59	< 0.05
FEV1/FVC, % predicted	— 0.63	< 0.01	— 0.49	NS

*NS = not significant.