Wilson S J, Wallin A, Della-Cioppa G, Sandström T, Holgate S T
Respiratory Cell and Molecular Biology Research Division, School of Medicine, University of Southampton, Southhampton, United Kingdom.
Am J Respir Crit Care Med. 2001 Sep 15;164(6):1047-52. doi: 10.1164/ajrccm.164.6.2010045.
The asthmatic inflammatory response can be attenuated by corticosteroids and in part by beta(2)-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF-kappaB), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF-kappaB, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF-kappaB, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappaB, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF-kappaB-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting beta(2)-agonists probably operates through alternative pathways.
哮喘炎症反应可被皮质类固醇部分地被β₂受体激动剂减弱。我们研究了这些作用是否伴随着核因子κB（NF-κB）的下调，NF-κB是一种转录因子，可调节过敏性炎症中表达的许多细胞因子和黏附分子基因。对特应性哮喘患者在使用福莫特罗、布地奈德或安慰剂治疗8周前后进行支气管活检。活检组织用乙二醇甲基丙烯酸酯处理，并进行免疫组织化学染色，检测嗜酸性粒细胞（作为炎症指标）、活化的和总的NF-κB、黏附分子以及细胞因子。布地奈德治疗后，黏膜下层总NF-κB、粒细胞巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子-α（TNF-α）染色的细胞数量显著减少，同时黏膜嗜酸性粒细胞以及内皮细胞中血管细胞黏附分子-1（VCAM-1）和上皮细胞中白细胞介素-8（IL-8）的表达也显著降低。福莫特罗治疗后，嗜酸性粒细胞和活化的NF-κB的上皮表达显著降低，但这些变化并未伴随着黏附分子或细胞因子免疫反应性的降低。我们得出结论，吸入性皮质类固醇的至少部分治疗效果是通过抑制NF-κB调节的基因表达介导的，而长效β₂受体激动剂对气道嗜酸性粒细胞增多的减少可能通过其他途径起作用。
