INTERLEUKIN-1-BETA AND INTERFERON-GAMMA DIFFERENTIALLY REGULATE RELEASE OF MONOCYTE CHEMOTACTIC PROTEIN-1 AND INTERLEUKIN-8 BY HUMAN BRONCHIAL EPITHELIAL-CELLS

Airway inflammation is characterized by an accumulation of activated l eukocytes. Bronchial epithelial cells may contribute to this process b y releasing chemokines and by expressing surface membrane molecules in volved in the adhesion and activation of the recruited leukocytes, In this study, we analyzed the effects of cytokines and glucocorticoids o n the release of monocyte chemotactic protein-1 (MCP-1), a potent chem oattractant for predominantly monocytes and lymphocytes, by human bron chial epithelial cells and compared this with the release of interleuk in-8 (IL-8), which potently attracts neutrophils. In addition, we anal yzed the effects of cytokines and glucocorticoids on the epithelial ex pression of intercellular adhesion molecule (ICAM)-1, CD40, and human leukocyte antigen (HLA) class II molecules. Primary cultures of human bronchial epithelial cells constitutively released MCP-1 and IL-8, IFN -gamma greatly increased MCP-1 release, which was accompanied by incre ased expression of MCP-1 mRNA and an increased monocyte chemotactic po tential. In contrast, IFN-gamma had no effect on the release of IL-8, but it did increase the epithelial expression of ICAM-1, CD40, and HLA class II molecules, IL-1 beta increased both MCP-1 and IL-8 release, and increased the expression of ICAM-1 and CD40, but not HLA class II molecules. Dexamethasone partially inhibited the cytokine-induced rele ase of MCP-1 and IL-8 and the expression of ICAM-1, CD40, and HLA clas s IT molecules by human bronchial epithelial cells, HLA class IT molec ules by human bronchial epithelial cells, Our results indicate that IF N-gamma and IL-1 beta differentially regulate the MCP-1 and IL-8 relea se by human bronchial epithelial cells. In addition, IL-1 beta and par ticularly IFN-gamma increase the expression of ICAM-1, HLA class II an d/or CD40 molecules, which are involved in the adhesion and possibly a ctivation of the recruited leukocytes, Finally, the beneficial effect of glucocorticoid therapy in airway inflammatory diseases may be media ted in part by inhibition of chemokine release and ICAM-1, CD40, and H LA class II expression by bronchial epithelial cells.