Tomasello Giovanni, Rodolico Vito, Zerilli Monica, Martorana Anna, Bucchieri Fabio, Pitruzzella Alessandro, Marino Gammazza Antonella, David Sabrina, Rappa Francesca, Zummo Giovanni, Damiani Provvidenza, Accomando Salvatore, Rizzo Manfredi, de Macario Everly Conway, Macario Alberto J L, Cappello Francesco
Dipartimento di Chirurgia Generale, d'Urgenza e Trapianti d'Organo, Università degli Studi di Palermo §Istituto Euro-Mediterraneo di Scienza e Tecnologia (IEMEST), Palermo, Italy.
Appl Immunohistochem Mol Morphol. 2011 Dec;19(6):552-61. doi: 10.1097/PAI.0b013e3182118e5f.
In an earlier work, the role of heat shock protein (Hsp60) in the pathogenesis of ulcerative colitis (UC) was suggested by its significant increase in the pathological mucosa parallel with an increase in inflammatory cells. More data in this direction are reported in this work. We analyzed by immunohistochemistry biopsies of colon tissue from 2 groups of patients with UC and treated with either 5-aminosalicylic acid (5-ASA) alone or in combination with a probiotic. We looked for inflammatory markers and Hsp60. Both the treatments were effective in reducing symptoms but the group treated with both 5-ASA and probiotics showed better clinical results. Amelioration of symptoms was associated with reduction of both inflammation and Hsp60, a reduction that was most marked in the group treated with 5-ASA and probiotics. The levels of Hsp60 positively correlated with those of CD68-positive cells, and double immunofluorescence showed a high index of colocalization of the chaperonin and CD68 in lamina propria. Immunoelectron microscopy showed that Hsp60-classically a mitochondrial protein-was abundantly also present in cytosol in biopsies taken at the time of diagnosis, but not after the treatment. Our data suggest that Hsp60 is an active player in pathogenesis of UC and it can be hypothesized that the chaperonin is responsible, at least in part, for initiation and maintenance of disease.
在早期的一项研究中，热休克蛋白（Hsp60）在溃疡性结肠炎（UC）发病机制中的作用被提出，因为其在病理黏膜中的显著增加与炎症细胞的增加平行。本研究报告了更多这方面的数据。我们通过免疫组织化学分析了两组UC患者的结肠组织活检样本，这些患者分别单独接受5-氨基水杨酸（5-ASA）治疗或5-ASA与益生菌联合治疗。我们寻找炎症标志物和Hsp60。两种治疗方法都能有效减轻症状，但接受5-ASA和益生菌联合治疗的组临床效果更好。症状的改善与炎症和Hsp60的减少相关，这种减少在接受5-ASA和益生菌治疗的组中最为明显。Hsp60的水平与CD68阳性细胞的水平呈正相关，双重免疫荧光显示伴侣蛋白和CD68在固有层中的共定位指数很高。免疫电子显微镜显示，Hsp60——经典地认为是一种线粒体蛋白——在诊断时采集的活检样本的细胞质中也大量存在，但治疗后则不存在。我们的数据表明，Hsp60是UC发病机制中的一个活跃参与者，可以推测伴侣蛋白至少部分负责疾病的起始和维持。
