Interferon-gamma and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts

The expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and more specifically vascular adhesion molecule-1 (VCAM-1) on lun g fibroblasts may be important for migration of inflammatory cells through the submucosa to the airway lumen in the asthmatic inflammatory response. T his study aimed to assess which cytokines are regulating ICAM-1 and VCAM-1 expression on human lung fibroblasts. For this purpose, confluent fibroblas t cultures (derived from lung tissue from a nonasthmatic donor) were stimul ated for 4 h with interleukin(IL)-1 beta, tumour necrosis factor (TNF)alpha , interferon (IFN)gamma, IL-4, IL-5 or transforming growth factor (TGF)beta . IL-1 beta (optimal concentration (OC) 1 U.mL(-1)) and TNF alpha (OC 100 U.m L(-1)) both increased ICAM-1 and VCAM-1 expression. IFN gamma (OC 2 U.mL(-1 )) increased only ICAM-1 expression and IL-4 (OC 5 ng.mL(-1)) increased onl y VCAM-1 expression, whereas IL-5 (20 ng.mL(-1)) and TGF beta (10 ng.mL(-1) ) did not influence ICAM-1 or VCAM-1 expression. ICAM-1 expression reached a plateau at 8-12 h after cytokine stimulation and remained constant for at least 24 h. VCAM-1 showed a transient increased expression within 24 h aft er IL-1 beta and TNF alpha stimulation. In contrast, VCAM-1 expression did not decrease after maximal expression at 4 h upon IL-4 stimulation. It is concluded that the Helper-1T-cell, type cytokine interferon gamma and the Helper-2 T-cell type cytokine interleukin-4 differentially regulate in tercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expre ssion on human lung fibroblasts. The proinflammatory cytokines interleukin- 1 beta and tumour necrosis factor alpha increase both intercellular adhesio n molecule-1 and vascular cell adhesion molecule-1 expression, without diff erential regulation of the expression of these adhesion molecules.