Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps.
Artikel i vetenskaplig tidskrift, 2004

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. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.

Författare

Mikael Benson

Göteborgs universitet

Lena M S Carlsson

Sahlgrenska Universitetssjukhuset

Mikael Adner

Malmo University Hospital

Margareta Jernås

Göteborgs universitet

Mats Rudemo

Chalmers, Institutionen för matematisk statistik

Göteborgs universitet

Anders Sjögren

Chalmers University of Technology

Per-Arne Svensson

Göteborgs universitet

Rolf Uddman

Malmo University Hospital

Lars Olaf Cardell

Malmo University Hospital

Journal of Allergy and Clinical Immunology

0091-6749 (ISSN) 1097-6825 (eISSN)

Vol. 113 1137-43

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1016/j.jaci.2004.02.028

PubMed

15208596