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蛋白酪氨酸激酶抑制剂可阻止单核细胞增生李斯特菌和伊氏李斯特菌进入上皮细胞。

Protein tyrosine kinase inhibitors block the entries of Listeria monocytogenes and Listeria ivanovii into epithelial cells.

作者信息

Velge P, Bottreau E, Kaeffer B, Yurdusev N, Pardon P, Van Langendonck N

机构信息

Laboratoire de Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique Tours-Nouzilly, France.

出版信息

Microb Pathog. 1994 Jul;17(1):37-50. doi: 10.1006/mpat.1994.1050.

DOI:10.1006/mpat.1994.1050
PMID:7861952
Abstract

The internalization of Listeria by intestinal epithelial cells is still poorly understood, however it is becoming apparent that microorganisms have developed the ability to interact with host cell receptor molecules to induce their own internalization. In this report we show that inhibition of cell tyrosine phosphorylation by protein tyrosine kinase (PTK) inhibitors blocks L. monocytogenes entry into both finite and immortalized intestinal cell lines. Some differences were observed between the Listeria species. L. monocytogenes entry was inhibited by between 10- to 100-fold by PTK inhibitors competing with the tyrosine residue binding of the kinase as erbstatin or by PTK inhibitors competing with the binding of ATP to the enzyme as genistein and some tyrphostins. On the other hand, L. ivanovii entry was inhibited by erbstatin as observed with L. monocytogenes but poorly by genistein and tyrphostins. The use of these several PTK inhibitors shows that even though both L. monocytogenes and L. ivanovii entered intestinal and other cell lines by stimulating PTK, it seems that L. monocytogenes stimulated a different PTK than L. ivanovii. According to the fact that the number of PTK receptors increases on immortalized cells, the higher L. monocytogenes internalization observed with immortalized cell lines could be related to a higher PTK receptor number on these cells compared to finite cell lines.

摘要

肠道上皮细胞对李斯特菌的内化作用仍未得到充分了解,然而,微生物已发展出与宿主细胞受体分子相互作用以诱导自身内化的能力,这一点正变得越来越明显。在本报告中,我们表明蛋白酪氨酸激酶(PTK)抑制剂对细胞酪氨酸磷酸化的抑制作用可阻止单核细胞增生李斯特菌进入有限传代和永生化的肠道细胞系。在李斯特菌的不同菌种之间观察到了一些差异。与激酶的酪氨酸残基结合竞争的PTK抑制剂(如埃博霉素)或与ATP与该酶的结合竞争的PTK抑制剂(如染料木黄酮和一些 tyrphostin)可使单核细胞增生李斯特菌的进入受到10至100倍的抑制。另一方面,埃博霉素可抑制伊氏李斯特菌的进入,这与单核细胞增生李斯特菌的情况相同,但染料木黄酮和tyrphostin对其抑制作用较弱。使用这些多种PTK抑制剂表明,尽管单核细胞增生李斯特菌和伊氏李斯特菌都是通过刺激PTK进入肠道和其他细胞系的,但单核细胞增生李斯特菌似乎刺激的是与伊氏李斯特菌不同的PTK。根据永生化细胞上PTK受体数量增加这一事实,与有限传代细胞系相比,在永生化细胞系中观察到的单核细胞增生李斯特菌更高的内化作用可能与这些细胞上更高的PTK受体数量有关。

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