Center of Biological and Health Sciences, State University of Pará, Belém, PA, Brazil.
Tropical Medicine Center, Federal University of Pará, Belém, PA, Brazil.
Dis Markers. 2018 Dec 16;2018:7067961. doi: 10.1155/2018/7067961. eCollection 2018.
causes leprosy, a dermatoneurological disease which affects the skin and peripheral nerves. One of several cellular structures affected during infection is the endoplasmic reticulum (ER). Infection by microorganisms can result in ER stress and lead to the accumulation of unfolded or poorly folded proteins. To restore homeostasis in the cell, the cell induces a series of signaling cascades known as the unfolded protein response called UPR (unfolded protein response). The present work is aimed at investigating the in situ expression of these markers in cutaneous lesions of clinical forms of leprosy and establish possible correlation expression patterns and types of lesion. A total of 43 samples from leprosy patients were analyzed by immunohistochemistry with monoclonal antibodies against GRP78/BiP, PERK, IRE1, and ATF6. A statistically significant difference between the indeterminate, tuberculoid, and lepromatous clinical forms was detected, with high expression of GRP78/BiP, PERK, IRE1, and ATF6 in tuberculoid forms (TT) when compared to lepromatous leprosy (LL) and indeterminate (I) leprosy. These results represent the first evidence of ER stress in samples of skin lesions from leprosy patients. We believe that they will provide better understanding of the complex pathogenesis of the disease and facilitate further characterization of the cascade of molecular events elicited during infection.
麻风分枝杆菌引起麻风,这是一种影响皮肤和周围神经的皮肤神经病。在感染过程中受影响的几种细胞结构之一是内质网(ER)。微生物感染可导致内质网应激,并导致未折叠或折叠不良的蛋白质积累。为了恢复细胞内的平衡,细胞会诱导一系列称为未折叠蛋白反应(UPR)的信号级联反应。本研究旨在调查这些标志物在麻风临床病变中的原位表达情况,并建立可能的表达模式和病变类型之间的相关性。通过免疫组织化学方法,用针对 GRP78/BiP、PERK、IRE1 和 ATF6 的单克隆抗体对 43 例麻风患者的样本进行了分析。在未定型、结核样和瘤型麻风的临床形式之间检测到统计学上的显著差异,与瘤型麻风(LL)和未定型(I)麻风相比,结核样麻风(TT)中 GRP78/BiP、PERK、IRE1 和 ATF6 的表达较高。这些结果代表了 ER 应激在麻风患者皮肤病变样本中的首次证据。我们相信,它们将有助于更好地理解该疾病的复杂发病机制,并促进对感染过程中引发的分子事件级联的进一步表征。