Role of Campylobacter jejuni gamma-glutamyl transpeptidase on epithelial cell apoptosis and lymphocyte proliferation
Role of Campylobacter jejuni gamma-glutamyl transpeptidase on epithelial cell apoptosis and lymphocyte proliferation
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DOI：
10.1186/1757-4749-6-20
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发表时间：
2014-06-12
期刊：
影响因子：
4.2
通讯作者：
Lehours, Philippe
中科院分区：
文献类型：
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作者：
Floch, Pauline;Pey, Vincent;Lehours, Philippe
背景：γ-谷氨酰转肽酶（GGT）由高达31%的空肠弯曲菌菌株产生。C.空肠GGT与幽门螺杆菌GGT接近，提示其活性保守，但与后者不同，C.空肠GGT尚未被广泛研究。与H. pylori中，我们的目的是纯化C.方法：采用C. jejuni GGT分离纯化大肠杆菌，并研究其对上皮细胞和人淋巴细胞的抑制和促凋亡活性。通过层析从培养物上清液中纯化空肠GGT。在通过使用纯化酶的质谱法验证纯度后，研究了其对两种上皮细胞系和人淋巴细胞的作用。细胞培养和流式细胞术实验的结果表明，C。空肠GGT与螺杆菌GGT相关，并抑制上皮细胞的增殖，而无促凋亡活性。C.空肠GGT还通过引起细胞周期停滞在G 0/G1期来抑制淋巴细胞增殖。这些作用在GGT的特异性药理学抑制剂的存在下被消除。空肠GGT活性与其它ε-变形杆菌GGT活性相当，更一般地与胆汁螺杆菌相当（抑制上皮细胞和淋巴细胞增殖，但无促凋亡活性）。因此，它可以被认为是一种致病因子，并通过抑制淋巴细胞增殖来促进细菌在宿主体内的持续存在。这些观察结果与这种酶在慢性感染的病理生理学中的作用一致。空肠。
Background: A gamma-glutamyl transpeptidase (GGT) is produced by up to 31% of strains of Campylobacter jejuni isolates. C. jejuni GGT is close to Helicobacter pylori GGT suggesting a conserved activity but unlike the latter, C. jejuni GGT has not been studied extensively. In line with the data available for H. pylori, our objectives were to purify C. jejuni GGT from the bacteria, and to evaluate its inhibitory and proapoptotic activities on epithelial cells and human lymphocytes.Methods: C. jejuni GGT was purified from culture supernatants by chromatography. After verification of the purity by using mass spectrometry of the purified enzyme, its action on two epithelial cell lines and human lymphocytes was investigated. Cell culture as well as flow cytometry experiments were developed for these purposes.Results: This study demonstrated that C. jejuni GGT is related to Helicobacter GGTs and inhibits the proliferation of epithelial cells with no proapoptotic activity. C. jejuni GGT also inhibits lymphocyte proliferation by causing a cell cycle arrest in the G0/G1 phase. These effects are abolished in the presence of a specific pharmacological inhibitor of GGT.Conclusion: C. jejuni GGT activity is comparable to that of other Epsilonproteobacteria GGTs and more generally to Helicobacter bilis (inhibition of epithelial cell and lymphocyte proliferation, however with no proapoptotic activity). It could therefore be considered as a pathogenicity factor and promote, via the inhibition of lymphocyte proliferation, the persistence of the bacteria in the host. These observations are consistent with a role of this enzyme in the pathophysiology of chronic infections associated with C. jejuni.