Interferon‐γ 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 lung fibroblasts may be important for migration of inflammatory cells through the submucosa to the airway lumen in the asthmatic inflammatory response. This study aimed to assess which cytokines are regulating ICAM‐1 and VCAM‐1 expression on human lung fibroblasts. For this purpose, confluent fibroblast cultures (derived from lung tissue from a nonasthmatic donor) were stimulated for 4 h with interleukin(IL)‐1β, tumour necrosis factor (TNF)α, interferon (IFN)γ, IL‐4, IL‐5 or transforming growth factor (TGF)β. IL‐1β (optimal concentration (OC) 1 U·mL ‐1 ) and TNFα (OC 100 U·mL ‐1 ) both increased ICAM‐1 and VCAM‐1 expression. IFNγ (OC 2 U·mL ‐1 ) increased only ICAM‐1 expression and IL‐4 (OC 5 ng·mL ‐1 ) increased only VCAM‐1 expression, whereas IL‐5 (20 ng·mL ‐1 ) and TGFβ (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 after IL‐1β and TNFα 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 γ and the Helper‐2 T‐cell type cytokine interleukin‐4 differentially regulate intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 expression on human lung fibroblasts. The proinflammatory cytokines interleukin‐1β and tumour necrosis factor α increase both intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 expression, without differential regulation of the expression of these adhesion molecules.