Benson Mikael, Carlsson Lena, Adner Mikael, Jernås Margareta, Rudemo Mats, Sjögren Anders, Svensson Per Arne, Uddman Rolf, Cardell Lars Olaf
Laboratory for Clinical and Experimental Allergy Research, Department of Oto-Rhino-Laryngology, Malmö University Hospital, Malmö, Sweden.
J Allergy Clin Immunol. 2004 Jun;113(6):1137-43. doi: 10.1016/j.jaci.2004.02.028.
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.
We sought to identify GC-regulated anti-inflammatory genes in nasal polyps.
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.
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.
Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.
局部使用糖皮质激素（GCs）治疗可减轻症状并减小鼻息肉大小。这可能取决于促炎基因的下调以及抗炎基因的上调。
我们试图鉴定鼻息肉中GC调节的抗炎基因。
使用Affymetrix DNA微阵列分析4例鼻息肉在局部使用氟替卡松（400μg/d）治疗前后22,283个基因的表达。采用实时PCR分析6例鼻息肉和6例健康对照者鼻活检标本中子宫珠蛋白和乳腺珠蛋白B的表达。
治疗后的息肉中有203个基因表达发生变化，其中139个具有已知功能：54个基因下调，85个基因上调。与炎症相关的基因构成最大的单一功能组。这些基因影响炎症的关键步骤（如免疫球蛋白产生、抗原加工和呈递以及粒细胞、T细胞和B细胞的趋化和激活）。一些促炎基因下调。相比之下，一些抗炎基因上调。表达增加最多的基因是子宫珠蛋白。这通过实时PCR得到证实。相比之下，未治疗息肉中子宫珠蛋白的表达低于健康鼻黏膜。免疫组织化学研究显示，对照者和鼻息肉的上皮及浆液黏液腺中有子宫珠蛋白染色。
抗炎基因如子宫珠蛋白的上调可能有助于局部使用GCs治疗鼻息肉的效果。
