Raqib R, Ljungdahl A, Lindberg A A, Wretlind B, Andersson U, Andersson J
Division of Clinical Bacteriology, Karolinska Institutet, Huddinge Hospital, Sweden.
Eur J Immunol. 1996 May;26(5):1130-8. doi: 10.1002/eji.1830260526.
In our study, infection with Shigella dysenteriae type 1 (n = 16) or Shigella flexneri in adults (n = 5) was associated with a gradual accumulation of mRNA for interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6, transforming growth factor-beta, IL-10, IL-4, TNF-beta, interferon (IFN)-gamma and perforin in the rectal biopsy samples during the convalescent stage of the disease demonstrated by in situ hybridization. In contrast, immunohistochemical staining in rectal tissues of cytokine protein-producing cells at the single-cell level exhibited a steady-state expression during 2-36 days after the onset of the disease. The frequency of cytokine mRNA-expressing cells varied in the range of 3-100-fold higher than that of the corresponding protein-synthesizing cells. The accumulation of cytokine mRNA in vivo during shigellosis represented a long-lasting phenomenon throughout the disease course, and may be linked to its immunopathogenesis. The results also indicate that assessment of both protein and mRNA in vivo may provide complementary information. Stimulation in vitro of peripheral blood mononuclear cells from normal healthy donors with Shigella-derived lipopolysaccharide or shiga toxin was carried out to elucidate the role of Shigella antigens in the regulation of translation of cytokine-specific mRNA. The incidence of cytokine (IFN-gamma, IL-6 and TNF-alpha) mRNA- and cytokine protein-expressing cells was very similar and congruent after both these Shigella-derived stimuli. We could, thus, not find evidence for shiga toxin-induced down-regulation of cytokine mRNA translation as the explanation for the observed discrepancy between cytokine mRNA and protein levels in the tissue biopsies.
在我们的研究中，1型痢疾志贺菌感染（n = 16）或成人福氏志贺菌感染（n = 5）与疾病恢复期直肠活检样本中白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α、IL-6、转化生长因子-β、IL-10、IL-4、TNF-β、干扰素（IFN）-γ和穿孔素的mRNA逐渐积累相关，这通过原位杂交得以证实。相比之下，疾病发作后2至36天期间，直肠组织中细胞因子蛋白产生细胞的单细胞水平免疫组化染色呈现稳态表达。细胞因子mRNA表达细胞的频率比相应蛋白质合成细胞的频率高3至100倍不等。志贺菌病期间体内细胞因子mRNA的积累在整个病程中是一种持久现象，可能与其免疫发病机制有关。结果还表明，体内蛋白质和mRNA的评估可能提供互补信息。对正常健康供体的外周血单核细胞进行体外刺激，用志贺菌衍生的脂多糖或志贺毒素刺激，以阐明志贺菌抗原在细胞因子特异性mRNA翻译调控中的作用。在这两种志贺菌衍生刺激后，细胞因子（IFN-γ、IL-6和TNF-α）mRNA表达细胞和细胞因子蛋白表达细胞的发生率非常相似且一致。因此，我们找不到证据表明志贺毒素诱导细胞因子mRNA翻译下调可解释组织活检中观察到的细胞因子mRNA和蛋白水平之间的差异。
