The glucocorticoid receptor gene as a candidate for gene therapy in asthma

Abstract

Glucocorticoids (GC) are commonly used as anti-inflamexpression vector. Using AP-1 and NF-B-dependent matory drugs in asthma, but can produce serious secondreporter gene assays and an immunoassay for the proary effects and, moreover, be inefficient in corticoresistant inflammatory cytokine RANTES, we show that the overasthmatics. After binding to the glucocorticoid receptor expressed GR significantly repressed AP-1 and NF-B (GR), they repress the synthesis of proinflammatory cytoactivities in the absence of hormone and that the GC kines via inhibition of the transcription factors AP-1 and NFdexamethasone produced an additive inhibitory effect. The B. Since qualitative and quantitative defects of the GR GC-independent repression of AP-1 and NF-B activities have been reported in corticoresistant patients, the transfer was further demonstrated by overexpressing a ligandof the GR gene in the lung epithelium, the primary site of binding deficient GR mutant. Our data suggest that delivery inflammation in asthma, may restore sensitivity to GC in of the GR gene in vivo may reduce inflammation without these patients. As a prerequisite to in vivo studies, we have recourse to GC and may constitute an alternative theratransfected A549 human lung epithelial cells with a GR peutic approach for corticoresistant asthma.

Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells

“…In fact, previous reports support the existence of ligand-independent effects of GR expression. In one study, overexpressed GR inhibited the activity of Nuclear factor-kB, and in further work, a similar conclusion was reached, even when a mutated GR was expressed with disrupted nuclear localization function (Mathieu et al, 1999;Doucas et al, 2000).…”

Genetic engineering of the glucocorticoid receptor by fusion with the herpes viral protein VP22 causes selective loss of transactivation

“…The proinflammatory actions of NF B are well characterised, and opposition of NF B by GR can explain many of the anti-inflammatory actions of glucocorticoids (Scheinman et al 1995b, Cato & Wade 1996, Nissen & Yamamoto 2000. Glucocorticoid sensitivity is related to GR expression (Vanderbilt et al 1987) and, furthermore, opposition of NF B action, and so anti-inflammatory activity, can be enhanced by overexpressing the GR (Mathieu et al 1999).…”

Dexamethasone Downregulates Chemokine Receptor CXCR4 and Exerts Neuroprotection against Hypoxia/Ischemia-Induced Brain Injury in Neonatal Rats

“…They inhibit the expression of proinflammatory cytokines [25], diminish astrocytic proliferation [26], but enhance certain immune responses during the later phase of inflammation [22]. Nothing is known about the possibility that some of the neuroprotective effects of DEX may be mediated by chemokines.…”

“…These authors suggested the preventive role of reduced glucose and phosphate utilization as one of the cardinal neuroprotective underlying mechanisms. However, other mediators involved in the protective action of DEX [24][25][26] are not yet fully understood.…”