Rhinitis, sinusitis, and ocular diseases
Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps

https://doi.org/10.1016/j.jaci.2004.02.028Get rights and content

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 μg/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.

Section snippets

Patients

Six male patients with bilateral nasal polyposis requiring surgical intervention (median age, 48 years; age range, 41-54 years) were included in this study (Table E1 in the Journal's Online Repository at www.mosby.com/jaci). In addition, nasal mucosal biopsy specimens were obtained from 6 healthy control subjects for examination with real-time PCR. Their median age was 31 years (range, 24-47 years), and 2 were women. Nasal polyposis was identified on the basis of clinical symptoms and the

General characteristics of the gene expression data

Nasal polyps before and after treatment with GCs were analyzed with duplicate DNA microarrays that measured the expression of 22,283 genes. The quality of the microarray data was assessed during various control experiments. This led to the exclusion of one of the patients (see the Methods section in the Journal's Online Repository at www.mosby.com/jaci). The reproducibility of the gene expression data for the remaining 3 patients was supported by good agreement between the duplicate

Discussion

In this study the expression of 22,283 genes was analyzed in nasal polyps before and after GC treatment. Of these genes, 203 differed in expression, and 139 had known functions. The largest functional group comprised genes related to inflammation. Several proinflammatory genes were downregulated. These affected key steps in inflammation, ranging from the influx of leukocytes to immunoglobulin production. Although most of these genes have not been previously described as GC regulated, their

References (40)

  • M. Maurer et al.

    Differential gene expression profile of glucocorticoids, testosterone, and dehydroepiandrosterone in human cells

    Horm Metab Res

    (2001)
  • P. Obexer et al.

    Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis

    Oncogene

    (2001)
  • M. Tonko et al.

    Gene expression profiles of proliferating vs. G1/G0 arrested human leukaemia cells suggest a mechanism for glucocorticoid-induced apoptosis

    FASEB J

    (2001)
  • L.C. Meagher et al.

    Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes

    J Immunol

    (1996)
  • M. Benson et al.

    DNA microarrays to study gene expression in allergic airways

    Clin Exp Allergy

    (2002)
  • B.G. Gabrielsson et al.

    Depot-specific expression of fibroblast growth factors in human adipose tissue

    Obes Res

    (2002)
  • B.G. Ohlsson et al.

    Oxidized low density lipoprotein inhibits lipopolysaccharide-induced binding of nuclear factor-kappaB to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1beta in macrophages

    J Clin Invest

    (1996)
  • J.I. Webster et al.

    Neuroendocrine regulation of immunity

    Annu Rev Immunol

    (2002)
  • V.G. Tusher et al.

    Significance analysis of microarrays applied to the ionizing radiation response

    Proc Nat Acad Sci

    (2001)
  • B. Efron et al.

    Empirical Bayes analysis of a microarray experiment

    J Am Stat Assoc

    (2001)

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    Supported by the Swedish Medical Research Council, Swegene; the Swedish Heart and Lung Foundation; the Lundberg Foundation and the Swedish Asthma and Allergy Foundation; and the Knut and Alice Wallenberg Foundation.

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    Copyright © 2004 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.