title: Interleukin-1beta and interferon-gamma differentially regulate release of monocyte chemotactic protein-1 and interleukin-8 by human bronchial epithelial cells.
abstract: Airway inflammation is characterized by an accumulation of activated leukocytes. Bronchial epithelial cells may contribute to this process by releasing chemokines and by expressing surface membrane molecules involved in the adhesion and activation of the recruited leukocytes. In this study, we analyzed the effects of cytokines and glucocorticoids on the release of monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant for predominantly monocytes and lymphocytes, by human bronchial epithelial cells and compared this with the release of interleukin-8 (IL-8), which potently attracts neutrophils. In addition, we analyzed the effects of cytokines and glucocorticoids on the epithelial expression 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 increased expression of MCP-1 mRNA and an increased monocyte chemotactic potential. 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-1beta 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 release of MCP-1 and IL-8 and the expression of ICAM-1, CD40, and HLA class II molecules by human bronchial epithelial cells. Our results indicate that IFN-gamma and IL-1beta differentially regulate the MCP-1 and IL-8 release by human bronchial epithelial cells. In addition, IL-1beta and particularly IFN-gamma increase the expression of ICAM-1, HLA class II and/or CD40 molecules, which are involved in the adhesion and possibly activation of the recruited leukocytes. Finally, the beneficial effect of glucocorticoid therapy in airway inflammatory diseases may be mediated in part by inhibition of chemokine release and ICAM-1, CD40, and HLA class II expression by bronchial epithelial cells.
authors.affiliation: Department of Immunology, Erasmus University and University Hospital Dijkzigt, Rotterdam, The Netherlands. vandervelden@immu.fgg.eur.nl
authors.forename: V H
authors.initials: VH
authors.lastname: van der Velden
authors.forename: M M
authors.initials: MM
authors.lastname: Verheggen
authors.forename: S
authors.initials: S
authors.lastname: Bernasconi
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
authors.forename: B A
authors.initials: BA
authors.lastname: Naber
authors.forename: C A
authors.initials: CA
authors.lastname: van der Linden-van Beurden
authors.forename: H C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: M
authors.initials: M
authors.lastname: Versnel
mesh_terms: D001980:Bronchi / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016133:Polymerase Chain Reaction
chemical_list: D019013:CD40 Antigens; D018932:Chemokine CCL2; D006681:HLA-D Antigens; D007375:Interleukin-1; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003907:Dexamethasone; D007371:Interferon-gamma; D007041:Hypoxanthine Phosphoribosyltransferase