Omar Usmani | PubMed Health

PubMed2002

Attenuated production of intracellular IL-10 and IL-12 in monocytes from patients with severe asthma.

Interleukin (IL)-10 and IL-12 production is decreased in peripheral blood mononuclear cells of patients with mild asthma. Using whole blood culture and flow cytometry we examined whether monocyte heterogeneity influenced IL-10 and IL-12 production in subjects with severe asthma. We demonstrated that IL-10 release in LPS-stimulated whole blood culture was decreased in patients with severe persistent asthma compared to those with mild asthma and controls (P = 0.04 and P < 0.001, respectively). In asthmatic patients, the percentage of CD14(+)CD16(+) cells was higher than that from normal subjects (P = 0.04). Severe asthmatics showed significantly less positive staining for IL-10 and IL-12 (P < 0.001 and P = 0.02, respectively) after stimulation in monocytes, compared to mild asthmatics and controls in both CD14(+)CD16(+) and CD14(+)CD16(minus sign) cells. These results suggest that IL-10 synthesis is attenuated in severe persistent asthma compared to mild asthma and that this cannot be explained by the increase in the CD14(+)CD16(+) monocytes in asthma.

Adult↗

PubMed2002

Molecular interactions between glucocorticoids and long-acting beta2-agonists.

beta(2)-Adrenergic receptor agonists and glucocorticoids are the two most effective treatments for asthma, and used in combination they are more effective than either alone. Glucocorticoids mediate their anti-inflammatory effects through the action of activated glucocorticoid receptors (GRs), with the level of activity being related to the number of nuclear receptors. Glucocorticoids can upregulate the synthesis of several genes in human lung cells through interaction with specific DNA binding regions (glucocorticoid response elements) within the promoter region of glucocorticoid-responsive genes. Many of the down-regulating effects of GRs on the synthesis of cytokines and other inflammatory mediators are due to repression of other transcription factors, such as activator protein-1 and nuclear factor kappaB. GR functions such as nuclear localization and gene activation can be regulated by phosphorylation status. Long-acting beta(2)-agonists may affect GR nuclear localization through modulation of GR phosphorylation and furthermore through priming of GR functions within the nucleus by modifying GR or GR-associated protein phosphorylation. Glucocorticoids in turn may regulate beta(2)-adrenergic receptor function by increasing its expression, acting through glucocorticoid response elements, and, importantly, by restoring G-protein-beta(2)-receptor coupling and inhibiting beta(2)-receptor downregulation, thereby preventing desensitization.

Adrenergic beta-2 Receptor Agonists↗