title: Anti-inflammatory mechanisms of glucocorticoids targeting granulocytes.
abstract: Asthmatic inflammation involves the recruitment and activation of inflammatory cells, and changes in the structural cells of the lung and asthma are characterized by an increased expression of components of the inflammatory cascade including cytokines, chemokines, growth factors, enzymes, receptors and adhesion molecules. The increased expression of these proteins seen in asthma is generally the result of enhanced gene transcription, since many of the genes are not expressed in normal cells but are induced in a cell-specific manner during the inflammatory process. There is clear evidence that neutrophils, long thought of as being transcriptionally inert, can respond to stimuli to induce inflammatory genes. Glucocorticoids are very effective in controlling the inflammation seen in asthmatic airways. Beyond their recognized actions on eosinophil and neutrophil apoptosis, glucocorticoids have profound effects on the chemotaxis, activation and release of mediators from granulocytes (eosinophils, neutrophils and basophils). Few mechanistic studies are available in these cells, but it appears that in granulocytes, glucocorticoids target the same signaling pathways, such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), that are important in other cells. We summarize these known mechanisms at the end of this review.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Science, Technology and Medicine, Dovehouse Street, London, SW3 6LY, UK. ian.adcock@imperial.ac.uk
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids