Modulation of ICAM-1 expression in human alveolar macrophages in vitro.
Modulation of intercellular adhesion molecule-1 (ICAM-1) expression may be a basic mechanism by which alveolar macrophages (AMs) regulate the inflammatory process in the lung in response to local stimuli. As a model for studying the anti-inflammatory activity of drugs on human AMs, we investigated the effects of fusafungine, an antibiotic for local use by aerosol with anti-inflammatory properties, and that of the glucocorticoid dexamethasone, on ICAM-1 expression induced in vitro by recombinant interferon-gamma (rIFN-gamma). ICAM-1 protein expression was studied on AMs by means of flow cytometry with an anti-CD54 monoclonal antibody; messenger ribonucleic acid (mRNA) levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ICAM-1 was expressed before culture on 21% of bronchoalveolar lavage (BAL) cells, with low intensity. Culture for 24 h with rIFN-gamma resulted in a significant increase in ICAM-1 protein expression (82% of cells were strongly positive). Fusafungine significantly inhibited rIFN-gamma-induced ICAM-1-protein expression on AMs in a concentration-dependent fashion. The mechanism of ICAM-1 downregulation was mainly post-transcriptional, but also partly transcriptional. By contrast, dexamethasone did not influence rIFN-gamma-induced ICAM-1 expression. This in vitro model using human AMs should prove useful for investigating the cellular and molecular targets of anti-inflammatory drugs.
Fattal-German
M
M
Laboratoire d'Immunologie CNRS URA 1159, Université Paris-XI, Hôpital Marie-Lannelongue, Le Plessis-Robinson, France.
Ladurie
F L
FL
Cerrina
J
J
Lecerf
F
F
Berrih-Aknin
S
S
D000336:Aerosols / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001483:Base Sequence; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D047630:Depsipeptides; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D005670:Fusarium; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D011994:Recombinant Proteins; D014158:Transcription, Genetic
D000336:Aerosols; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D047630:Depsipeptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; C014001:fusafungin; D003907:Dexamethasone; D007371:Interferon-gamma; D012194:RNA-Directed DNA Polymerase