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.

Effects of lactose-β-sitosterol and β-sitosterol on ovalbumin-induced lung inflammation in actively sensitized mice

“…Clinical and review studies demonstrated that the treatment of asthma with corticosteroids inhibits the infiltration of eosinophils and lymphocytes in the bronchial mucosa and diminishes Th2 cytokine expression [24,25]. Dexamethasone blocked eosinophil recruitment into lung, and Th2 cytokine and IgE expression (Figs.…”

Establishment of an allergic rhinitis model in mice for the evaluation of nasal symptoms

“…Ketotifen, an antiallergy drug having H1-receptor antagonist activity, is widely used for allergic disease and known to be effective in reducing sneezing (Grant et al, 1990). Glucocorticoid is also widely used in the treatment of inflammatory disease, including allergic inflammation (Caramori and Adcock, 2005). Thus we evaluated the effects of ketotifen and dexamethasone on our model of allergic rhinitis in B10.S mice.…”

Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis

“…Treatment with AP-1 or NF-kB decoy ODN significantly decreased IL-1b, TNF-a, and MPO activities in the tissue contents, which coincided well with the results of our histological examinations (Figure 6a-c). [33][34][35][36][37][38][39][40] Although AP-1 is a major immunoregulatory as well as proinflammatory transcription factor, 21,[27][28][29][30][45][46][47] nothing is known to have been reported regarding the effect of AP-1 inhibition by a decoy ODN on intestinal inflammation. In the present study, we designed a ds decoy ODN binding to AP-1-specific nucleotide sequences and investigated its efficacy to prevent murine experimental DSS-induced colitis.…”