title: Fibroblast-eosinophil interaction: modulation of adhesion molecules expression and chemokine release by human fetal lung fibroblasts in response to IL-4 and TNF-alpha.
abstract: In addition to be involved in airway remodelling observed in asthmatic patients, lung fibroblasts may directly contribute to pulmonary inflammation through the release of mediators and through the expression of surface molecules involved in cell-cell interaction. The aim of the study was to evaluate whether two cytokines involved in asthma pathogenesis, IL-4 and TNF-alpha, could modulate the expression of adhesion molecules (VCAM-1 and ICAM-1) and the secretion of chemokines (eotaxin and MCP-1) related to eosinophil recruitment and activation. The constitutive expression of VCAM-1 by unstimulated fibroblasts was over 2-fold lower than that of ICAM-1 (P<0.05). Significant differences were also observed in the release of chemokines by unstimulated fibroblast, the levels of eotaxin being over 17-fold lower than those of MCP-1. Stimulation of the cells with IL-4 or TNF-alpha induced a dose-dependent increase in VCAM-1, while ICAM-1 was overexpressed only in culture stimulated by TNF-alpha (P<0.05) but not in those exposed to IL-4 (P>0.05 each comparison). In contrast, a significant increase in MCP-1 and eotaxin release was observed in the presence of TNF-alpha (P<0.05) but not of IL-4 (P>0.05). These data show that two 'proinflammatory' cytokines, such as IL-4 and TNF-alpha, may have different and complementary effects on functions involved in the cross-talking between fibroblasts and eosinophils.
authors.affiliation: Pulmonary Division, G. Gaslini Institute, Largo G. Gaslini5, 16147 Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sabatini
authors.forename: Michela
authors.initials: M
authors.lastname: Silvestri
authors.forename: Rosa
authors.initials: R
authors.lastname: Sale
authors.forename: Lucia
authors.initials: L
authors.lastname: Scarso
authors.forename: Anna-Carla
authors.initials: AC
authors.lastname: Defilippi
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Risso
authors.forename: Giovanni A
authors.initials: GA
authors.lastname: Rossi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001249:Asthma / Q000209:etiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D015847:Interleukin-4 / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D019742:Chemokines, CC; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4