Regulation of glucocorticoid receptor mRNA in nasal mucosa by local administration of fluticasone and budesonide.
The glucocorticoid receptor (GR) is downregulated by glucocorticoids (autoregulation). In contrast, the metallothionein gene (MTIIa) is positively regulated by glucocorticoids, which requires a functional receptor protein. We have investigated the expression of GR and MTIIa mRNA in nasal mucosal biopsy specimens, nasal brush-lavage samples, and peripheral blood lymphocytes from 14 healthy volunteers after local treatment with one of two different glucocorticoids: fluticasone propionate or budesonide. In nasal mucosal biopsy specimens, a significant decrease in GR mRNA occurred with increasing doses of both steroids, whereas a significant and parallel increase in MTIIa mRNA was observed. We found nasal brush-lavage less suitable for studies of GR mRNA and MTIIa mRNA regulation by locally administered glucocorticoids. In mucosal biopsy specimens, but not in peripheral blood lymphocytes, we found a correlation between basal GR mRNA and MTIIa mRNA levels, where low GR mRNA levels were associated with low MTIIa mRNA levels, and vice versa. In conclusion, this study shows that locally administered glucocorticoids significantly affect the expression of specific genes and that there is an interindividual and tissue-specific variation in GR mRNA and MTIIa mRNA expression, which may be used in studies of variations in clinical responses to nasal glucocorticoids.
Knutsson
P U
PU
Department of Otorhinolaryngology, Karolinska Institute, Huddinge University Hospital, Sweden.
Brönnegård
M
M
Marcus
C
C
Stierna
P
P
D000287:Administration, Topical; D000730:Androstadienes / Q000008:administration & dosage* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001706:Biopsy; D019819:Budesonide; D015536:Down-Regulation / Q000187:drug effects; D000068298:Fluticasone; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids; D006801:Humans; D008668:Metallothionein / Q000235:genetics; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology; D011282:Pregnenediones / Q000008:administration & dosage* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D007507:Therapeutic Irrigation
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D019819:Budesonide; D008668:Metallothionein; D000068298:Fluticasone