Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps.
BACKGROUND
Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes.


OBJECTIVE
We sought to identify GC-regulated anti-inflammatory genes in nasal polyps.


METHODS
Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects.


RESULTS
Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps.


CONCLUSIONS
Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.
Benson
Mikael
M
Laboratory for Clinical and Experimental Allergy Research, Department of Oto-Rhino-Laryngology, Malmö University Hospital, Malmö, Sweden.
Carlsson
Lena
L
Adner
Mikael
M
Jernås
Margareta
M
Rudemo
Mats
M
Sjögren
Anders
A
Svensson
Per Arne
PA
Uddman
Rolf
R
Cardell
Lars Olaf
LO
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D060788:Mammaglobin B; D008875:Middle Aged; D009185:Myelin Proteins; D009298:Nasal Polyps / Q000188:drug therapy* / Q000378:metabolism*; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011510:Proteolipids; D060765:Secretoglobins; D014598:Uteroglobin / Q000032:analysis / Q000235:genetics*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D060788:Mammaglobin B; D009185:Myelin Proteins; D009363:Neoplasm Proteins; D011510:Proteolipids; C556467:SCGB2A1 protein, human; D060765:Secretoglobins; D014598:Uteroglobin